A kainate receptor-selective RNA aptamer.

Kainate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are two major, closely related receptor subtypes in the glutamate ion channel family. Excessive activities of these receptors have been implicated in a number of central nervous system diseases. Designing potent and selective antagonists of these receptors, especially of kainate receptors, is useful for developing potential treatment strategies for these neurological diseases. Here, we report on two RNA aptamers designed to individually inhibit kainate and AMPA receptors. To improve the biostability of these aptamers, we also chemically modified these aptamers by substituting their 2'-OH group with 2'-fluorine. These 2'-fluoro aptamers, FB9s-b and FB9s-r, were markedly resistant to RNase-catalyzed degradation, with a half-life of ∼5 days in rat cerebrospinal fluid or serum-containing medium. Furthermore, FB9s-r blocked AMPA receptor activity. Aptamer FB9s-b selectively inhibited GluK1 and GluK2 kainate receptor subunits, and also GluK1/GluK5 and GluK2/GluK5 heteromeric kainate receptors with equal potency. This inhibitory profile makes FB9s-b a powerful template for developing tool molecules and drug candidates for treatment of neurological diseases involving excessive activities of the GluK1 and GluK2 subunits.

Characterization of suspended membrane waveguides towards a photonic atom trap integrated platform.

We demonstrate an optical waveguide device, capable of supporting the high, in-vacuum, optical power necessary for trapping a single atom or a cold atom ensemble with evanescent fields. Our photonic integrated platform, with suspended membrane waveguides, successfully manages optical powers of 6 mW (500 µm span) to nearly 30 mW (125 µm span) over an un-tethered waveguide span. This platform is compatible with laser cooling and magneto-optical traps (MOTs) in the vicinity of the suspended waveguide, called the membrane MOT and the needle MOT, a key ingredient for efficient trap loading. We evaluate two novel designs that explore critical thermal management features that enable this large power handling. This work represents a significant step toward an integrated platform for coupling neutral atom quantum systems to photonic and electronic integrated circuits on silicon.

Frequency Conversion in a Time-Variant Dielectric Metasurface.

The color of light is a fundamental property of electromagnetic radiation; as such, control of the frequency is a cornerstone of modern optics. Nonlinear materials are typically used to generate new frequencies, however the use of time-variant systems provides an alternative approach. Utilizing a metasurface that supports a high-quality factor resonance, we demonstrate that a rapidly shifting refractive index will induce frequency conversion of light that is confined in the nanoresonator meta-atoms. We experimentally observe this frequency conversion and develop a time-dependent coupled mode theory model that well describes the system. The intersection of high quality-factor resonances, active materials, and ultrafast transient spectroscopy leads to the demonstration of metasurfaces operating in a time-variant regime that enables enhanced control over light-matter interaction.

Identification and characterization of RNA aptamers: A long aptamer blocks the AMPA receptor and a short aptamer blocks both AMPA and kainate receptors.

AMPA and kainate receptors, along with NMDA receptors, represent different subtypes of glutamate ion channels. AMPA and kainate receptors share a high degree of sequence and structural similarities, and excessive activity of these receptors has been implicated in neurological diseases such as epilepsy. Therefore, blocking detrimental activity of both receptor types could be therapeutically beneficial. Here, we report the use of an in vitro evolution approach involving systematic evolution of ligands by exponential enrichment with a single AMPA receptor target (i.e. GluA1/2R) to isolate RNA aptamers that can potentially inhibit both AMPA and kainate receptors. A full-length or 101-nucleotide (nt) aptamer selectively inhibited GluA1/2R with a KI of ∼5 µm, along with GluA1 and GluA2 AMPA receptor subunits. Of note, its shorter version (55 nt) inhibited both AMPA and kainate receptors. In particular, this shorter aptamer blocked equally potently the activity of both the GluK1 and GluK2 kainate receptors. Using homologous binding and whole-cell recording assays, we found that an RNA aptamer most likely binds to the receptor's regulatory site and inhibits it noncompetitively. Our results suggest the potential of using a single receptor target to develop RNA aptamers with dual activity for effectively blocking both AMPA and kainate receptors.

Integrated photonic encoder for low power and high-speed image processing.

Modern lens designs are capable of resolving greater than 10 gigapixels, while advances in camera frame-rate and hyperspectral imaging have made data acquisition rates of Terapixel/second a real possibility. The main bottlenecks preventing such high data-rate systems are power consumption and data storage. In this work, we show that analog photonic encoders could address this challenge, enabling high-speed image compression using orders-of-magnitude lower power than digital electronics. Our approach relies on a silicon-photonics front-end to compress raw image data, foregoing energy-intensive image conditioning and reducing data storage requirements. The compression scheme uses a passive disordered photonic structure to perform kernel-type random projections of the raw image data with minimal power consumption and low latency. A back-end neural network can then reconstruct the original images with structural similarity exceeding 90%. This scheme has the potential to process data streams exceeding Terapixel/second using less than 100 fJ/pixel, providing a path to ultra-high-resolution data and image acquisition systems.

Multi-site integrated optical addressing of trapped ions.

One of the most effective ways to advance the performance of quantum computers and quantum sensors is to increase the number of qubits or quantum resources in the system. A major technical challenge that must be solved to realize this goal for trapped-ion systems is scaling the delivery of optical signals to many individual ions. In this paper we demonstrate an approach employing waveguides and multi-mode interferometer splitters to optically address multiple 171Yb+ ions in a surface trap by delivering all wavelengths required for full qubit control. Measurements of hyperfine spectra and Rabi flopping were performed on the E2 clock transition, using integrated waveguides for delivering the light needed for Doppler cooling, state preparation, coherent operations, and detection. We describe the use of splitters to address multiple ions using a single optical input per wavelength and use them to demonstrate simultaneous Rabi flopping on two different transitions occurring at distinct trap sites. This work represents an important step towards the realization of scalable integrated photonics for atomic clocks and trapped-ion quantum information systems.

Comparison of the Analgesic Duration Using Ultrasound-guided Popliteal Sciatic Nerve Block between Diabetics with Neuropathy and Nondiabetics without Neuropathy.

INTRODUCTION: In India, the prevalence of diabetes mellitus neuropathy was reported to be as high as 30%. Eight percentage of the diabetic population suffer from foot ulceration and 1.8% have amputations. Popliteal nerve block can be potentially used for foot and ankle surgery with several advantages. AIM: To compare analgesic duration of an ultrasound (US)-guided popliteal sciatic nerve block between diabetics with neuropathy and nondiabetics without neuropathy. PATIENTS AND METHODS: Participants were allocated into two groups for popliteal sciatic nerve blocks under US guidance. The primary outcome was the duration to onset of sensory and motor blockade. The secondary outcome was the duration to rescue analgesic and the visual analog scale scoring within 24 h. Hemodynamic outcomes were also monitored along with the above variables. RESULTS: It was observed that the onset of sensory blockade was faster in participants with diabetes mellitus with peripheral neuropathy as compared to the nondiabetic participants and the duration for onset of motor blockade in dorsiflexion was faster in diabetic patients as compared to the nondiabetic patients (17.48 ± 3.21 min). However, there was no significant changes when comparing the onset of duration to loss of plantar flexion, in diabetics (17.86 ± 2.29 min) versus in nondiabetics (18.51 ± 3.32 min). The duration for rescue analgesics was found to be longer in diabetic participants (13.19 ± 2.14 h) as compared to the nondiabetic participants (11.44 ± 1.86 h). No differences were observed in the hemodynamic changes and the complications associated with local anesthetics in either group. CONCLUSION: Diabetic patients with neuropathy have faster onset of blockade when compared to nondiabetic patients without neuropathy which may be due to the degenerative condition of the peripheral nerves in them. The hemodynamic parameters do not play a role in defining the outcome of the block.

Résumé Introduction:En Inde, la prévalence de la neuropathie liée au diabète sucré atteignait 30 %. Huit pour cent de la population diabétique souffrent d'ulcères du pied et 1,8 % sont amputés. Le bloc du nerf poplité peut être potentiellement utilisé pour la chirurgie du pied et de la cheville avec plusieurs avantages.Objectif:Comparer la durée analgésique d'un bloc du nerf sciatique poplité guidé par échographie (É.-U.) entre des diabétiques atteints de neuropathie et des non diabétiques sans neuropathie.Patients et méthodes:Les participants ont été répartis en deux groupes pour les blocs du nerf sciatique poplité sous la direction des États-Unis. Le critère de jugement principal était la durée jusqu'à l'apparition du blocus sensoriel et moteur. Le résultat secondaire était la durée nécessaire pour sauver l'analgésique et l'échelle visuelle analogique après 24 h. Les résultats hémodynamiques ont également été surveillés avec les variables ci-dessus.Résultats:Il a été observé que l'apparition du blocage sensoriel était plus rapide chez les participants atteints de diabète sucré avec neuropathie périphérique que chez les participants non diabétiques et (la durée d'apparition du blocage moteur en dorsiflexion était plus rapide chez les patients diabétiques que chez les patients non diabétiques (Cependant, il n'y a eu aucun changement significatif en comparant le début de la durée à la perte de flexion plantaire, chez les diabétiques (17,86 ± 2,29 min) versus chez les non diabétiques (18,51 ± 3,32 min). La durée des analgésiques de secours a été trouvée être plus longue chez les participants diabétiques (13,19 ± 2,14 h) par rapport aux participants non diabétiques (11,44 ± 1,86 h). Aucune différence n'a été observée dans les changements hémodynamiques et les complications associées aux anesthésiques locaux dans les deux groupes.Conclusion:Patients diabétiques atteints de neuropathie ont un début de blocage plus rapide que les patients non diabétiques sans neuropathie, ce qui peut être dû à l'état dégénératif des nerfs périphériques chez eux. Les paramètres hémodynamiques ne jouent aucun rôle dans la définition de l'issue du bloc.

Volume-dependent dose-response of the intestinal stem cell niche and lymphoid tissue.

BACKGROUND AND PURPOSE: Plasticity of the intestinal stem cell compartment in response to radiation injury is regulated by a stem cell niche. We present here the first experimental observations of a dose-volume effect of the intestinal stem cell niche and of the solitary intestinal lymphoid tissues (SILT). MATERIALS AND METHODS: Regeneration of intestinal crypts in mice was studied following irradiation of millimetre-size jejunal sections with single doses of 6 to 24 Gy and compared to total body irradiation (TBI). The statistical distribution of cells per crypt was scored and regressed to a biomathematical model. The number of SILTs was scored for different doses and field sizes and crypt regeneration was correlated with SILT proximity. RESULTS: We observed a differential dose-response of the intestinal stem cell niche at the centres of the irradiated sections, but only for field sizes below 10 mm. Irradiation of 5 mm jejunum results in an increase in crypt survival by up to an order of magnitude, compared to TBI. Distributions of cell-per-crypt numbers and comparison to biomathematical modelling suggest that these observations stem from a field size-dependent regeneration rate. The density of SILTs also exhibits a volume-dependent dose-response and increased crypt survival correlates with a proximity to SILTs. CONCLUSION: Our findings present the first observation of a field-size dependent dose-response of the intestinal stem cell niche. Its regeneration process does apparently not rely on distant radiation-sensitive resources of the organism, such as the bone marrow. Yet, our observations suggest that the niche interacts with intact tissue in millimetres distance, leading to faster crypt regeneration. The field-size dependent dose-response of SILTs posits a role of the immune system on the dose-volume effect.

Frequency-division multiplexer and demultiplexer for terahertz wireless links.

The development of components for terahertz wireless communications networks has become an active and growing research field. However, in most cases these components have been studied using a continuous or broadband-pulsed terahertz source, not using a modulated data stream. This limitation may mask important aspects of the performance of the device in a realistic system configuration. We report the characterization of one such device, a frequency multiplexer, using modulated data at rates up to 10 gigabits per second. We also demonstrate simultaneous error-free transmission of two signals at different carrier frequencies, with an aggregate data rate of 50 gigabits per second. We observe that the far-field spatial variation of the bit error rate is different from that of the emitted power, due to a small nonuniformity in the angular detection sensitivity. This is likely to be a common feature of any terahertz communication system in which signals propagate as diffracting beams not omnidirectional broadcasts.There is growing interest in the development of components to facilitate wireless communications in the terahertz but the characterization of these systems involve an unmodulated input. Here the authors demonstrate multiplexing and demultiplexing of data streams in the terahertz range using a real data link.

One aptamer, two functions: the full-length aptamer inhibits AMPA receptors, while the short one inhibits both AMPA and kainate receptors.

AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels. Excessive activity of AMPA and kainate receptors has been implicated in neurological diseases, such as epilepsy and neuropathic pain. Antagonists that block their activities are therefore potential drug candidates. In a recent article in the Journal of Biological Chemistry by Jaremko et al. 2017, we have reported on the discovery and molecular characterization of an RNA aptamer of a dual functionality: the full-length RNA (101 nucleotide) inhibits AMPA receptors while the truncated or the short (55 nucleotide) RNA inhibits both the AMPA and kainate receptors. The full-length RNA aptamer was isolated through a specially designed, systematic evolution of ligands by exponential enrichment (SELEX) using only a single type of AMPA receptors expressed in HEK-293 cells. The design feature and the results of our recent article are highlighted here, as they demonstrate the utility of the SELEX approach and the potential of using a single AMPA receptor type to develop potent, novel RNA aptamers targeting multiple subunits and AMPA/kainate receptor subtypes with length-dependent functionalities.

Terahertz Artificial Dielectric Lens.

We have designed, fabricated, and experimentally characterized a lens for the THz regime based on artificial dielectrics. These are man-made media that mimic properties of naturally occurring dielectric media, or even manifest properties that cannot generally occur in nature. For example, the well-known dielectric property, the refractive index, which usually has a value greater than unity, can have a value less than unity in an artificial dielectric. For our lens, the artificial-dielectric medium is made up of a parallel stack of 100 µm thick metal plates that form an array of parallel-plate waveguides. The convergent lens has a plano-concave geometry, in contrast to conventional dielectric lenses. Our results demonstrate that this lens is capable of focusing a 2 cm diameter beam to a spot size of 4 mm, at the design frequency of 0.17 THz. The results further demonstrate that the overall power transmission of the lens can be better than certain conventional dielectric lenses commonly used in the THz regime. Intriguingly, we also observe that under certain conditions, the lens boundary demarcated by the discontinuous plate edges actually resembles a smooth continuous surface. These results highlight the importance of this artificial-dielectric technology for the development of future THz-wave devices.

Studies in hawaiian Diptera I: new distributional records for endemic asteia (asteiidae).

New island records are reported for five species of Asteia endemic to the Hawaiian Islands (Asteiahawaiiensis, Asteiamauiensis, Asteiamolokaiensis, Asteiapalikuensis, Asteiasabroskyi). These new records expand our understanding of distributions in Asteia, change the percentage of single island endemics from 78% to 33%, and have significance in how we view the process of diversification acting in this lineage. We also present a list of the known rearing records for two species in this group. Asteiamontgomeryi has been recorded from Erythrina and Asteiasabroskyi has been reared from Pisonia, Urera, Charpentiera and Hibiscadelphus.