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Background: In meningiomas, CDKN2A/B deletions are associated with poor outcomes but are rare in most cohorts (1-5%). Large molecular datasets are therefore required to explore these deletions and their relationship to other prognostic CDKN2A alterations. Methods: We utilized multidimensional molecular data of 560 meningiomas from 5 independent cohorts to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Results: Meningiomas with either CDKN2A/B deletions (partial or homozygous loss) or an intact CDKN2A gene locus but elevated mRNA expression (CDKN2Ahigh) both had poor clinical outcomes. Increased CDKN2A mRNA expression was a poor prognostic factor independent of CDKN2A deletion. CDKN2A expression and p16 protein increased with tumor grade and more aggressive molecular and methylation groups. CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycling pathways dysregulated at different checkpoints. p16 immunohistochemistry was unreliable in differentiating between meningiomas with and without CDKN2A deletions, but increased positivity was associated with increased mRNA expression. CDKN2Ahigh meningiomas were associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. Conclusions: These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications.
There is significant interest in developing early passage cell lines with matched normal reference DNA to facilitate a precision medicine approach in assessing drug response. This study aimed to establish early passage cell lines, and perform whole exome sequencing and short tandem repeat profiling on matched normal reference DNA, primary tumour and corresponding cell lines.
Methods
A cell culture based, in vitro study was conducted of patients with primary human papillomavirus positive and human papillomavirus negative tumours.
Results
Four early passage cell lines were established. Two cell lines were human papillomavirus positive, confirmed by sequencing and p16 immunoblotting. Short tandem repeat profiling confirmed that all cell lines were established from their index tumours. Whole exome sequencing revealed that the matched normal reference DNA was critical for accurate mutational analysis: a high rate of false positive mutation calls were excluded (87.6 per cent).
Conclusion
Early passage cell lines were successfully established. Patient-matched reference DNA is important for accurate cell line mutational calls.
Piezoelectric AlGaN/GaN FETs on SiC with high carrier mobility have been fabricated yielding IDS=450 mA/mm and gm=200 mS/mm. In the on-state, under UV-illumination, the devices sustain a drain voltage of VDS=49 V, corresponding to a power dissipation of 26.5 W/mm. On turn-on of the device from the pinch-off state, a significant delay in the drain current build-up is observed. This effect depends on the pinch-off time and the pinch-off voltage and can be removed by either a brief UV-illumination or a VDS>25 V applied in the on-state. The drain current transients are characterized by a relaxation time τ, which is in the order of several hundred seconds. From the temperature dependence of τ, an activation energy of about 280 meV and a capture cross section of 4.4·10−18cm2 were determined. The devices show pronounced persistent photoconductivity (PPC) and the drain current ID is sensitive to illumination.
A method is presented for fabricating fully wet-etched InGaN/GaN laser cavities using hotoenhanced electrochemical wet etching followed by crystallographic wet etching. Crystallographic wet chemical etching of n- and p-type GaN grown on c-plane sapphire is achieved using H3PO4 and various hydroxides, with etch rates as high as 3.2.μm/min. The crystallographic GaN etch planes are {0001}, {100}, {10}, {10}, and {103}. The vertical {100} planes appear perfectly smooth when viewed with a field-effect scanning electron microscope (FESEM), indicating a surface roughness less than 5 nm, suitable for laser facets. The etch rate and crystallographic nature for the various etching solutions are independent of conductivity, as shown by seamless etching of a p-GaN/undoped, high-resistivity GaN homojunction.
A method is presented for fabricating fully wet-etched InGaN/GaN laser cavities using photoenhanced electrochemical wet etching followed by crystallographic wet etching. Crystallographic wet chemical etching of n- and p-type GaN grown on c-plane sapphire is achieved using H3PO4 and various hydroxides, with etch rates as high as 3.2 μm/min. The crystallographic GaN etch planes are {0001}, {1010}, {1011}, {1012}, and {1013}. The vertical {1010} planes appear perfectly smooth when viewed with a field-effect scanning electron microscope (FESEM), indicating a surface roughness less than 5 nm, suitable for laser facets. The etch rate and crystallographic nature for the various etching solutions are independent of conductivity, as shown by seamless etching of a p-GaN/undoped, high-resistivity GaN homojunction.
We report on fabrication and characterization of cleaved laser facets and photoelectrochemically wet etched laser facets in III-Nitrides grown by MOVPE on c-plane sapphire. The roughness of the cleaved facets in the InGaN/GaN double heterostructure (DH) laser cavities with a 1000-Å-thick active region is ≈25 rim, while that of the wet etched GaN facets is ≈100 nm. A theoretical model is developed for the maximum allowable laser facet roughness, which yields a value of 18 nrm for uncoated GaN and 22 rm for the uncoated DH. Optically pumped laser action at room temperature is demonstrated in the cleaved DH laser cavities. 2 Above the incident threshold pumping power of 1.3 MW/cm2, the differential quantum efficiency increases by a factor of 34, the emission linewidth decreases to 13.5 meV, and the output becomes highly TE polarized. Wet chemical etching a 1-mm-long laser cavity into the GaN homostructure is found to increase the differential quantum efficiency by a factor of 2.
We report on the growth of InGaN films, and the fabrication and characterization of GaN homojunction LEDs and InGaN double heterostructure (DH) LEDs on HVPE GaNon- sapphire substrates. The use of these substrates facilitates the III-nitrides growth process, as it avoids the use of complicated buffer layers. We have achieved InGaN films with strong and sharp band-to-band photoluminescence (PL) from 370 to 540 nm. Typical In 0.o9Ga0. g9N/GaN DH films had double-crystal XRD FWHM ∼ 300 arcsec, and 400 nm peak PL emission with FWHM ∼ 100 meV. DH-LEDs were fabricated with InGaN layers with various compositions, and produced strong electroluminescence (EL) in the blue and blue/green regions.
The development of high quality indium based III-nitride compounds is lagging behind the corresponding aluminum and gallium based compounds. Potential problems confronting the growth of epitaxial and double heterostructure InGaN will be discussed. A mass balance model is presented describing the competing reaction pathways occurring during the growth of indium containing compounds. Atomic layer epitaxy and metalorganic chemical vapor deposition grown InGaN films will be used to explain this model. Also, the growth parameters leading to the attainment of high InN percentages, reduced indium metal formation, and improved structural and optical properties of indium containing nitrides will be discussed.
The emission wavelength of the InxGa1−xN ternary system can span from the near ultraviolet through red regions of the visible spectrum. High quality double heterostructures with these InxGa1−xN active layers are essential in the development of efficient optoelectronic devices such as high performance light emitting diodes and laser diodes. We will report on the MOCVD growth and characterization of thick and thin InGaN films. Thick InxGa1−xN films with values of x up to 0.40 have been deposited and their photoluminescence (PL) spectra measured. AlGaN/InGaN/AlGaN double heterostructures (DHs) have been grown that exhibit PL emission in the violet, blue, green and yellow spectral regions, depending on the growth conditions of the thin InGaN active layer. Preliminary results of an AllnGaN/InGaN/AllnGaN DH, with the potential of realizing a near-lattice matched structure, will also be presented.
InGaN based optical devices can cover from the violet through orange regions of the visible spectrum. Difficulties in the growth of this alloy, which have impeded its applications, include problems such as the high vapor pressure of In, weak In-N bonds and lack of sufficient nitrogen during growth. We report on the MOCVD growth of InxGa1−xN (0 < x < 0.4) on sapphire substrates in the 750 - 800 °C temperature range. X-ray diffraction data show full width at half maximum line widths as narrow as 250 arcsec for low values of x, while films with higher lnN% exhibit broader line widths. Room temperature photoluminescence spectra exhibit band edge emission, with emission from deep levels increasing with x. Preliminary investigations of AlGaN/lnGaN/AlGaN double heterostructures have been conducted.
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