Combined SIRT3 and SIRT5 deletion is associated with inner retinal dysfunction in a mouse model of type 1 diabetes

Abstract Diabetic retinopathy (DR) is a major cause of blindness in working adults in the industrialized world. In addition to vision loss caused by macular edema and pathological angiogenesis, DR patients often exhibit neuronal dysfunction on electrophysiological testing, suggesting that there may be an independent neuronal phase of disease that precedes vascular disease. Given the tremendous metabolic requirements of the retina and photoreceptors in particular, we hypothesized that derangements in metabolic regulation may accelerate retinal dysfunction in diabetes. As such, we induced hyperglycemia with streptozotocin in mice with monoallelic Nampt deletion from rod photoreceptors, mice lacking SIRT3, and mice lacking SIRT5 and tested multiple components of retinal function with electroretinography. None of these mice exhibited accelerated retinal dysfunction after induction of hyperglycemia, consistent with normal-appearing retinal morphology in hyperglycemic Sirt3 −/− or Sirt5 −/− mice. However, mice lacking both SIRT3 and SIRT5 (Sirt3 −/− Sirt5 −/− mice) exhibited significant evidence of inner retinal dysfunction after induction of hyperglycemia compared to hyperglycemic littermate controls, although this dysfunction was not accompanied by gross morphological changes in the retina. These results suggest that SIRT3 and SIRT5 may be involved in regulating neuronal dysfunction in DR and provide a foundation for future studies investigating sirtuin-based therapies

Compositional modulation in AlxGa1−xAs epilayers grown by molecular beam epitaxy on the (111) facets of grooves in a nonplanar substrate

We report the first observation of a lateral junction formed in an alloy due to an abrupt transition from segregated to random AlGaAs alloy compositions. Al0.25Ga0.75As epilayers were grown by molecular beam epitaxy on [011-bar] oriented grooves in a nonplanar (100) GaAs substrate. A quasi-periodic modulation of the aluminum concentration occurs spontaneously in material grown on the (111) facets of the groove, with a period of 50–70 Å along the [111] direction. The compositional modulation is associated with a reduction of the band gap by 130 meV, with respect to the random alloy. While segregation of the AlGaAs alloy has been seen previously, this is the first observation of segregation of AlGaAs grown on a (111) surface. The compositional modulation terminates abruptly at the boundaries of the (111) facet, forming abrupt lateral junctions in the AlGaAs layers grown on a groove

Millimeter-wave diode-grid phase shifters

Monolithic diode grids have been fabricated on 2-cm square gallium-arsenide wafers with 1600 Schottky-barrier varactor diodes. Shorted diodes are detected with a liquid-crystal technique, and the bad diodes are removed with an ultrasonic probe. A small-aperture reflectometer that uses wavefront division interference was developed to measure the reflection coefficient of the grids. A Phase shift of 70° with a 7-dB loss was obtained at 93 GHz when the bias on the diode grid was changed from -3 V to 1 V. A simple transmission-line grid model, together with the measured low-frequency parameters for the diodes, was shown to predict the measured performance over the entire capacitive bias range of the diodes, as well as over the complete reactive tuning range provided by a reflector behind the grid, and over a wide range of frequencies form 33 GHz to 141 GHz. This shows that the transmission-line model and the measured low-frequency diode parameters can be used to design an electronic beam-steering array and to predict its performance. An electronic beam-steering array made of a pair of grids using state-of-the-art diodes with 5-Ω series resistances would have a loss of 1.4 dB at 90 GHz

Millimeter-Wave Diode-Grid Frequency Doubler

Monolithic diode grid were fabricated on 2-cm^2 gallium-arsenide wafers in a proof-of-principle test of a quasi-optical varactor millimeter-wave frequency multiplier array concept. An equivalent circuit model based on a transmission-line analysis of plane wave illumination was applied to predict the array performance. The doubler experiments were performed under far-field illumination conditions. A second-harmonic conversion efficiency of 9.5% and output powers of 0.5 W were achieved at 66 GHz when the diode grid was pumped with a pulsed source at 33 GHz. This grid had 760 Schottky-barrier varactor diodes. The average series resistance was 27 Ω, the minimum capacitance was 18 fF at a reverse breakdown voltage of -3 V. The measurements indicate that the diode grid is a feasible device for generating watt-level powers at millimeter frequencies and that substantial improvement is possible by improving the diode breakdown voltage

A Coronal Hole's Effects on CME Shock Morphology in the Inner Heliosphere

We use STEREO imagery to study the morphology of a shock driven by a fast coronal mass ejection (CME) launched from the Sun on 2011 March 7. The source region of the CME is located just to the east of a coronal hole. The CME ejecta is deflected away from the hole, in contrast with the shock, which readily expands into the fast outflow from the coronal hole. The result is a CME with ejecta not well centered within the shock surrounding it. The shock shape inferred from the imaging is compared with in situ data at 1 AU, where the shock is observed near Earth by the Wind spacecraft, and at STEREO-A. Shock normals computed from the in situ data are consistent with the shock morphology inferred from imaging.Comment: to appear in The Astrophysical Journa

Histologic and Clinical Follow-up of Thyroid Fine Needle Aspirates in Pediatric Patients

BACKGROUND Although fine-needle aspiration (FNA) has an important role in evaluating thyroid nodules in adults, there is little published information regarding its utility in the pediatric population. METHODS A retrospective analysis of thyroid FNAs for patients who were 18 years old or younger at 2 institutions was conducted. Aspirates were retrospectively categorized with the Bethesda System for Reporting Thyroid Cytopathology. These diagnoses were then correlated with either final histopathology or clinical follow-up. RESULTS A total of 186 thyroid FNA samples from 154 patients (122 females and 32 males), who ranged in age from 9 months to 18 years (median, 16 years; mean, 14 years), were identified. FNA was performed to evaluate 1 to 3 nodules for each patient. Aspirates were classified as follows: nondiagnostic (n = 27), benign (n = 114), atypia of undetermined significance (AUS; n = 21), follicular neoplasm (FN; n = 8), suspicious for malignancy (n = 3), and malignant (n = 13). Sixty-one samples had a histologic correlation, 68 were followed clinically for ≥2 years, and 57 either had no follow-up or were followed for <2 years. For statistical purposes, FNA diagnoses of suspicious and malignant were considered positive, and benign lesions were considered negative. The accuracy was 99%, and the sensitivity and specificity were 94% and 100%, respectively. The risk of malignancy, not including papillary microcarcinoma, was 2% for benign aspirates, 21% for AUS, 57% for FN, and 100% for suspicious or malignant aspirates. CONCLUSIONS This analysis demonstrates that FNA is a sensitive and highly specific modality for evaluating thyroid nodules in pediatric patients. Each diagnostic category can facilitate communication and guide appropriate management

Time-Dependent Physicochemical Changes of Carbonate Surfaces from SmartWater (Diluted Seawater) Flooding Processes for Improved Oil Recovery.

Over the past few decades, field- and laboratory-scale studies have shown enhancements in oil recovery when reservoirs, which contain high-salinity formation water (FW), are waterflooded with modified-salinity salt water (widely referred to as the low-salinity, dilution, or SmartWater effect for improved oil recovery). In this study, we investigated the time dependence of the physicochemical processes that occur during diluted seawater (i.e., SmartWater) waterflooding processes of specific relevance to carbonate oil reservoirs. We measured the changes to oil/water/rock wettability, surface roughness, and surface chemical composition during SmartWater flooding using 10-fold-diluted seawater under mimicked oil reservoir conditions with calcite and carbonate reservoir rocks. Distinct effects due to SmartWater flooding were observed and found to occur on two different timescales: (1) a rapid (&lt;15 min) increase in the colloidal electrostatic double-layer repulsion between the rock and oil across the SmartWater, leading to a decreased oil/water/rock adhesion energy and thus increased water wetness and (2) slower (&gt;12 h to complete) physicochemical changes of the calcite and carbonate reservoir rock surfaces, including surface roughening via the dissolution of rock and the reprecipitation of dissolved carbonate species after exchanging key ions (Ca2+, Mg2+, CO32-, and SO42- in carbonates) with those in the flooding SmartWater. Our experiments using crude oil from a carbonate reservoir reveal that these reservoir rock surfaces are covered with organic-ionic preadsorbed films (ad-layers), which the SmartWater removes (detaches) as flakes. Removal of the organic-ionic ad-layers by SmartWater flooding enhances oil release from the surfaces, which was found to be critical to increasing the water wetness and significantly improving oil removal from carbonates. Additionally, the increase in water wetness is further enhanced by roughening of the rock surfaces, which decreases the effective contact (interaction) area between the oil and rock interfaces. Furthermore, we found that the rate of these slower physicochemical changes to the carbonate rock surfaces increases with increasing temperature (at least up to an experimental temperature of 75 °C). Our results suggest that the effectiveness of improved oil recovery from SmartWater flooding depends strongly on the formation of the organic-ionic ad-layers. In oil reservoirs where the ad-layer is fully developed and robust, injecting SmartWater would lead to significant removal of the ad-layer and improved oil recovery