Heterogeneous integration of a GaN-based photonic integrated circuit with an Si-based transimpedance amplifier.

The heterogeneous integration of a GaN-based photonic integrated circuit (PIC) and an Si-based transimpedance amplifier (TIA) is demonstrated in this work. The monolithic GaN PIC, fabricated from a GaN-on-Si light-emitting diode (LED) wafer, comprises LEDs whose optical outputs are coupled to photodetectors (PD) through suspended waveguides. The PIC chip is mounted onto a printed circuit board together with a TIA chip and two filter chip capacitors, occupying a compact footprint. The components are interconnected directly using wire-bonds to minimize signal delays and attenuation. The integrated system achieves rise and fall times of 2.21 and 2.10 ns, respectively, a transmission delay of 3.54 ns, and a bandwidth exceeding 390 MHz. Transmission of a pseudorandom binary sequence-3 (PRBS-3) signal across the integrated system is also demonstrated at the data transmission rate of 280 Mbit/s with a clearly resolved open eye diagram.

Isolation of Streptomycin-Resistant Erwinia pyrifoliae in Korea.

As a black shoot blight disease-causing agent, Erwinia pyrifoliae was first reported in 1995 in Korea. A total of 101 isolates of E. pyrifoliae were isolated from samples showing bacterial symptoms collected from apple and pear orchards between 2020 and 2021. These isolates were screened for streptomycin resistance, with one from an orchard in Gwangju showing resistance at 100 µg/ml streptomycin. This streptomycin-resistant E. pyrifoliae (EpSmR) isolate was identified via polymerase chain reaction amplification of the strA/strB gene and an internal region of the ribosomal rpsL gene containing codon 43. EpSmR has a point mutation that altered this codon from lysine (AAA) to threonine (ACA). The strA and strB genes were not identified in EpSmR. EpSmR showed a high resistance to streptomycin (>50,000 µg/ml). This is the first study reporting EpSmR, which emerged due to a mutation in codon 43 of the rpsL gene.

Whispering-gallery mode InGaN microdisks on GaN substrates.

Microdisks fabricated with III-nitride materials grown on GaN substrates are demonstrated, taking advantage of the high material quality of homoepitaxial films and advanced micro-fabrication processes. The epitaxial structure consists of InGaN/GaN multi-quantum wells (MQWs) sandwiched between AlGaN/GaN and InAlN/GaN superlattices as cladding layers for optical confinement. Due to lattice-matched growth with low dislocations, an internal quantum efficiency of ∼40% is attained, while the sidewalls of the etched 8 µm-diameter microdisks patterned by microsphere lithography are optically smooth to promote the formation of whispering-gallery modes (WGMs) within the circular optical cavities. Optically pumped lasing with low threshold of ∼5.2 mJ/cm2 and quality (Q) factor of ∼3000 at the dominant lasing wavelength of 436.8 nm has been observed. The microdisks also support electroluminescent operation, demonstrating WGMs consistent with the photoluminescence spectra and with finite-difference time-domain (FDTD) simulations.

Packaging of InGaN stripe-shaped light-emitting diodes.

We demonstrate the fabrication of InGaN/GaN stripe-shaped light-emitting diodes (LEDs) in flip-chip packaging (FC-LED) and vertically mounted packaging (VM-LED). Compared to conventionally packaged LEDs, these packaging schemes enhance light output and emission divergence in ways favorable for general lighting applications. The FC-LED can sustain efficiency at high current operations due to effective heat sinking, while the VM-LED excels at light extraction efficiency due to the exposure of two large emission surfaces. Together with the properties of low luminous exitance and emission uniformity, the stripe-shaped LEDs are ideal for the assembly of luminaires. An LED light tube comprising a continuous linear array of 10 stripe-shaped LED chips has been assembled. The optical performance of the light tube is compared to another light tube assembled with conventional square-shaped LED chips (with and without external diffuser) by confocal microscopy. It is found that emission uniformity of the stripe-shaped LED tube is significantly improved, with a threefold increase in illumination area, without efficiency loss associated with diffusers.

Paternal age as an independent factor does not affect embryo quality and pregnancy outcomes of testicular sperm extraction-intracytoplasmic sperm injection in azoospermia.

This study was performed to evaluate the independent influence of paternal age affecting embryo development and pregnancy using testicular sperm extraction (TESE)-intracytoplasmic sperm injection (ICSI) in obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). Paternal patients were divided into the following groups: ≤30 years, 31-35 years, 36-40 years, 41-45 years and ≥46 years. There were no differences in the rates of fertilisation or embryo quality according to paternal and maternal age. However, clinical pregnancy and implantation rates were significantly lower between those ≥46 years of paternal age compared with other age groups. Fertilisation rate was higher in the OA than the NOA, while embryo quality, pregnancy and delivery results were similar. Clinical pregnancy and implantation rates were significantly lower for patients ≥46 years of paternal age compared with younger age groups. In conclusion, fertilisation using TESE in azoospermia was not affected by the independent influence of paternal age; however, as maternal age increased concomitantly with paternal age, rates of pregnancy and delivery differed between those with paternal age <41 years and ≥46 years. Therefore, paternal age ≥46 years old should be considered when applying TESE-ICSI in cases of azoospermia, and patients should be advised of the associated low pregnancy rates.

Fabrication of Patterned Superhydrophobic/Hydrophilic Substrates by Laser Micromachining for Small Volume Deposition and Droplet-Based Fluorescence.

The deposition of nanoliter and subnanoliter volumes is important in chemical and biochemical droplet-based microfluidic systems. There are several techniques that have been established for the deposition/generation of small volumes including the use of surfaces with patterned differences in wettability. Many such methods require complex and time-consuming lithographic techniques. Here, we present a facile method for the fabrication of superhydrophobic surfaces with patterned hydrophilic regions by laser micromachining. A comprehensive study of fabrication parameters (laser machining speed, laser power, and patch size) on the material, patch wettability, and droplet volume is presented. Patch sizes as small as 100 µm diameter and as large as 1500 µm diameter were investigated, and volumes as low as 400 pL were observed. As an example application of such patterned materials and the deposition of small volumes, halide salts were preconcentrated on the hydrophilic patches, and their fluorescence quenching constants were rapidly calculated using a 3D-printed device coupled to a fluorescence spectrometer.

Flexible Free-Standing III-Nitride Thin Films for Emitters and Displays.

The majority of a GaN light-emitting diode (LED) is released from its sapphire substrate through selective-area laser lift-off to form a freely suspended light emitter. By virtue of being suspended in air without supporting substrates, the ultrathin crystalline and crack-free film possesses flexibility and bendability. The free-standing LEDs benefit from significant relaxation of strain, evident from red-shifting of the E2(high) phonon frequencies as measured by Raman spectroscopy toward those of strain-free free-standing GaN substrates. The phonon frequencies remain invariant upon bending of the film; this indicates that the properties of the flexible device will not be dependent on the bending curvatures. The observation of pronounced spectral blue-shifts from the photoluminescence (PL) spectrum from the flexible regions further confirms the occurrence of strain relaxation in the quantum wells. Being free-standing and thus lacking a direct heat-sinking pathway, emissions from the different regions of the suspended film can be affected by thermal effects to different extents, which are investigated by long-wave infrared thermometry. Heat accumulation is determined to be most severe at the far end of the flexible stripe at higher currents, leading to reduced efficiencies and electroluminescence (EL) spectral red-shifts. Based on this architecture, a monolithic 3 × 4 dot-matrix microdisplay prototype is demonstrated, comprising three adjacent flexible stripe emitters with four individually addressable pixels on each stripe. This proof-of-concept demonstration opens up new opportunities for GaN optoelectronics for a wide range of flexible display and visual applications.

Ageing-related changes in GABAergic inhibition in mouse auditory cortex, measured using in vitro flavoprotein autofluorescence imaging.

KEY POINTS: Ageing is associated with hearing loss and changes in GABAergic signalling in the auditory system. We tested whether GABAergic signalling in an isolated forebrain preparation also showed ageing-related changes. A novel approach was used, whereby population imaging was coupled to quantitative pharmacological sensitivity. Sensitivity to GABAA blockade was inversely associated with age and cortical thickness, but hearing loss did not independently contribute to the change in GABAA ergic sensitivity. Redox states in the auditory cortex of young and aged animals were similar, suggesting that the differences in GABAA ergic sensitivity are unlikely to be due to differences in slice health. To examine ageing-related changes in the earliest stages of auditory cortical processing, population auditory cortical responses to thalamic afferent stimulation were studied in brain slices obtained from young and aged CBA/CAj mice (up to 28 months of age). Cortical responses were measured using flavoprotein autofluorescence imaging, and ageing-related changes in inhibition were assessed by measuring the sensitivity of these responses to blockade of GABAA receptors using bath-applied SR95531. The maximum auditory cortical response to afferent stimulation was not different between young and aged animals under control conditions, but responses to afferent stimulation in aged animals showed a significantly lower sensitivity to GABA blockade with SR95531. Cortical thickness, but not hearing loss, improved the prediction of all imaging variables when combined with age, particularly sensitivity to GABA blockade for the maximum response. To determine if the observed differences between slices from young and aged animals were due to differences in slice health, the redox state in the auditory cortex was assessed by measuring the FAD+/NADH ratio using fluorescence imaging. We found that this ratio is highly sensitive to known redox stressors such as H2 O2 and NaCN; however, no difference was found between young and aged animals. By using a new approach to quantitatively assess pharmacological sensitivity of population-level cortical responses to afferent stimulation, these data demonstrate that auditory cortical inhibition diminishes with ageing. Furthermore, these data establish a significant relationship between cortical thickness and GABAergic sensitivity, which had not previously been observed in an animal model of ageing.

Whispering gallery mode lasing in optically isolated III-nitride nanorings.

III-nitride nanorings fabricated from a combination of hybrid-nanosphere-lithography and laser lift-off processes is demonstrated. Being formed on an interfacial metallic layer optically coupling between the optical ring and its substrate is eliminated, maximizing optical confinement of whispering gallery resonant mode within the ring cavity. The tapered cross-sectional profile also promotes coupling of emitted light into resonant modes. Optically pumped lasing with a dominant peak at 421.5 nm is observed at room temperature, with threshold energy density of ∼6.5 mJ/cm2. Etch-induced sidewall roughness causes scattering of light at the interface to diminish confinement, and is also responsible for the mode-splitting effect according to finite-difference time-domain simulations.

InGaN light-emitting diode stripes with reduced luminous exitance.

InGaN light-emitting diodes of stripe geometries have been demonstrated. The elongated geometry facilitates light spreading in the longitudinal direction. The chips are further shaped by laser-micromachining to have partially-inclined sidewalls. The light extraction efficiencies of such 3D chip geometries are enhanced by ~12% (~8% according to ray-trace simulations), leading to a reduction of junction temperatures. The effective emission area is also increased four times compared to a cubic chip. The stripe LEDs are thus more efficient emitters with reduced luminous exitance, making them more suitable for a wide range of lighting applications.

Novel technique for characterizing prostate cancer utilizing MRI restriction spectrum imaging: proof of principle and initial clinical experience with extraprostatic extension.

BACKGROUND: Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI). METHODS: We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique. RESULTS: 27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients. CONCLUSIONS: In this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.

Whispering-gallery mode lasing from optically free-standing InGaN microdisks.

Optically pumped multi-mode whispering-gallery mode (WGM) lasing has been observed in optically free-standing InGaN/GaN quantum well microdisks at room temperature. The ∼6.6 µm optically isolated microdisks are patterned by microsphere lithography on GaN thin-films prepared by laser lift-off of the sapphire substrate, enabling superior optical confinement. The modes are determined to be of second order according to simulations. The lasing threshold is found to be ∼9.06 mJ/cm2, with a quality factor Q of ∼770 evaluated from the dominant mode at λ=430.2 nm, and a free space range (FSR) of 3.17 to 2.16 nm, which is mode-dependent.

Geographic predictors of primary multidrug-resistant tuberculosis cases in an endemic area of Lima, Peru.

SETTING: Peru reports among the highest multidrug-resistant tuberculosis (MDR-TB) rates in the Americas, with a growing proportion in previously untreated tuberculosis (TB) cases. The identification of clusters of primary MDR-TB compared with drug-susceptible TB (DS-TB) could help prioritize interventions. OBJECTIVE: To examine the clustering of primary MDR-TB case residences and their proximity to high-risk locations in San Juan de Lurigancho District, Lima, Peru. DESIGN: Enrolled primary MDR-TB and primary DS-TB cases were interviewed and their primary residence was recorded using handheld Global Positioning System devices. Kuldorff's spatial scan statistic was used for cluster detection (SaTScan(TM), v. 9.1.1). Identified clusters were visualized in Quantum Geographic Information Systems software (v1.8.0). The following cluster centers were tested: a health centre with the highest TB and MDR-TB rates (Clinic X), a hospital and two prisons. Using regression analyses, we examined predictors of primary MDR-TB cases. RESULTS: A statistically significant cluster of primary MDR-TB cases was identified within a 2.29 km radius around Clinic X. Proximity to Clinic X remained a significant predictor of primary MDR-TB in adjusted regression analyses. CONCLUSION: We identified a hotspot of primary MDR-TB cases around Clinic X in a TB-endemic area. Causes of this clustering require investigation; targeted interventions for this high-risk area should be considered.

Cerium oxide-deposited mesoporous silica nanoparticles for the determination of carcinoembryonic antigen in serum using inductively coupled plasma-mass spectrometry.

CeO2-deposited mesoporous silica nanoparticles were synthesized as a probe to determine carcinoembryonic antigen (CEA) in serum by inductively coupled plasma-mass spectrometry (ICP-MS). The prepared mesoporous nanoparticles were modified and tagged to the target for sandwich-type immunoassay. Fe3O4 magnetic nanoparticles (MNPs) were also synthesized and immobilized with antibody to extract the target biomarker. The calibration curve of the synthesized CeO2-deposited silica nanoparticles, which was plotted by the signal ratio of (140)Ce/(57)Fe measured by ICP-MS vs. the concentration of CEA, showed excellent linearity and sensitivity owing to the signal amplification and low spectral interference. Under optimal conditions, the sandwich-type analytical method was applied to determine CEA in serum spiked in the range of 0.001-5 ng mL(-1) and showed a limit of detection of 0.36 ng mL(-1). Since the deposited CeO2 in the mesoporous silica layer can be substituted by other metal compounds, various kinds of metal-deposited nanoparticles can be prepared as probe materials for multiplex detection in bioanalysis.

Combination therapy with hepatocyte growth factor and oseltamivir confers enhanced protection against influenza viral pneumonia.

Frequent outbreaks caused by influenza viruses pose considerable public health threats worldwide. Virus-inflicted alveolar damage represents a major contributor of acute lung injury in influenza. We have previously demonstrated that hepatocyte growth factor (HGF) produced by macrophages enhances alveolar epithelial proliferation during influenza infection. Here, we investigated the therapeutic efficacy of recombinant human HGF (rhHGF) and an antiviral agent (oseltamivir) alone or in combination to treat influenza viral pneumonia in macrophage-depleted BALB/c mice. Combination therapy of infected mice significantly reduced lung pathology and mortality compared to other animal groups that received either treatment alone. Combination treatment with rhHGF induced alveolar type II (AT2) epithelial hyperplasia more prominently in the distal airways, evident by increased cells with double-positive staining for surfactant protein-C and proliferating cell nuclear antigen within the alveolar epithelial lining. Similarly, rhHGF supplementation also induced stem cell antigen-1 (SCA-1) transcriptional expression at 5 days post-infection (dpi), but mRNA levels of both SCA-1 and its receptor c-KIT were decreased by 10 dpi. Microarray and pathway analyses indicated that rhHGF administration may act by accelerating tissue repair and suppressing inflammatory processes to minimize damage by infection and to restore lung function by earlier repair. These results reveal that transient administration of rhHGF may confer synergistic effects in enhancing pulmonary repair by promoting AT2 cell proliferation. Thus, the combination of rhHGF and oseltamivir may represent a promising therapeutic option against influenza pneumonia to improve existing antiviral treatment regimens.

Application of bone marrow samples for discrimination of acute promyelocytic leukemia from other types of acute leukemia using the routine automated hematology analyzer.

INTRODUCTION: Unreported parameters produced by automated blood cell counter, particularly large unstained cells (LUC) and delta neutrophil index (DNI), indicated the presence of immature and possibly abnormal cell populations in white blood cell population. The purpose of this study was to investigate the laboratory performance for discrimination of acute promyelocytic leukemia (APL) cells from other types of leukemia cells and clinical value of LUC and DNI parameters in bone marrow (BM) samples of patients with acute leukemia. METHODS: A total of 73 BM samples of patients with various type of acute leukemia were analyzed. LUC and DNI parameters were determined by an automated hematology analyzer (ADVIA 120; Siemens Healthcare Diagnostics, New York, NY, USA). Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U methods. Receiver operating characteristic curve (ROC) analysis, survival analysis, and Cox proportional hazard model were used to evaluate the clinical implication. RESULTS: There were significant differences (P < 0.05) between APL group and other group in the DNI and LUC values except for DNI between APL group and non-APL myeloid leukemia group. The area under curve of LUC was larger than that of DNI from the ROC analysis for discrimination between APL group and other group. High LUC value was associated with the increased risk of adverse outcomes and the worse overall survival in patients with acute leukemia. CONCLUSION: Delta neutrophil index and LUC in BM showed discriminating power of APL cells from other leukemia cells.

First Report of Fusarium succisae Causing Flower Rot on Thread-leaf Coreopsis.

In July 2010, flower rot of thread-leaf coreopsis (Coreopsis verticillata) was found in a garden in the Icheon City, Korea. The disease affected about 20 to 50% of a 100 m2 area. The disease was characterized by the appearance of pinkish mycelia on the stigmata and inflorescences of flowers. In some cases, flowers failed to bloom or turned brown before opening fully. Fragments (each 5 × 5 mm) of the symptomatic tissue were surface-sterilized with 1% NaOCl for 1 min, and then rinsed twice in sterilized distilled water. The tissue pieces were placed on water agar (WA) and incubated at 25°C for 4 to 6 days. Twenty-two isolates of Fusarium species were obtained from the diseased flowers. All isolates were identified as Fusarium succisae based on their morphological characteristics on carnation leaf agar (CLA) medium and DNA sequences of the translation elongation factor 1-alpha gene (1). Macroconidia and sporodochia were sparsely produced on CLA medium. Microconidia were abundant, borne in false heads, oval or allantoid and sometimes pyriform, and measured 4.2 to 13 × 2.2 to 5.4 µm. Chlamydospores were absent. The EF-1α gene was amplified from three isolates by PCR assay and the amplification products were sequenced (2). The nucleotide sequences obtained were deposited in GenBank with accession numbers KF514658, KF514659, and KF514660. BLASTn analysis showed 99% homology with the EF-1α sequence of F. succisae NRRL13613 (GenBank Accession No. AF160291). Pathogenicity tests were conducted with inoculation of flowers on Coreopsis verticillata. Spore suspension was prepared by flooding 7-day-old cultures on potato dextrose agar with sterilized 2% (w/v) sugar solution. When the plants started to have buds, the isolates were inoculated by placing one drop (20 µl) of spore suspension (1 × 106 spores ml-1) into the buds. Fifteen buds of the plants were arranged into three replications. The control was treated with sterilized 2% sugar solution. Inoculated plants were kept in a greenhouse at 25/20°C (12 h/12 h). Three weeks after inoculation, the symptoms were observed on buds with mycelial production. Control plants had no mycelia on buds. F. succisae was re-isolated from the inoculated flowers. To our knowledge, this is the first report of flower rot of thread-leaf coreopsis caused by F. succisae. References: (1) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Blackwell Publishing, Ames, IA, 2006. (2) K. O'Donnell et al. Proc. Nat. Acad. Sci. 95:2044, 1998.