Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Optical properties of DNA-CTMA biopolymers and applications in metal-biopolymer-metal photodetectors

The potential of using a DNA biopolymer in an electro-optic device is presented. A complex of DNA with the cationic surfactant cetyltrimethylammonium-chloride (CTMA) was used to obtain an organic-soluble DNA material (DNA-CTMA). Poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) was added to the DNACTMA to increase the electrical conductivity of the biopolymer. The CW absorbance and time-resolved photoluminescence of the resulting DNA-CTMA and DNA-CTMA-PEDOT:PSS were investigated. Both DNA materials have absorbance peaks at ~260 nm and a broad, Stokes shifted, photoluminescence peak around 470nm. The photoluminescence lifetime of the materials was observed to decrease with increasing UV excitation. Specifically, excitation with a high power ultrafast (~150fs) UV (266nm) laser pulse resulted in a drastic decrease in the photoluminescence lifetime decreases after a few minutes. Moreover, the observed decrease was faster in an air ambient than in a nitrogen ambient. This is most likely due to photo-oxidation that degrades the polymer surface resulting in an increase in the non-radiative recombination. In order to investigate the photoconductivity of these two materials, metal-biopolymer-metal (MBM) ultraviolet photodetectors with interdigitated electrodes were fabricated and characterized. The photoresponsivity of these devices was limited by the transport dynamics within the film. The prospects for the use of these materials in optical devices will be discussed

Optical properties of DNA-CTMA biopolymers and applications in metal-biopolymer-metal photodetectors

The potential of using a DNA biopolymer in an electro-optic device is presented. A complex of DNA with the cationic surfactant cetyltrimethylammonium-chloride (CTMA) was used to obtain an organic-soluble DNA material (DNA-CTMA). Poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) was added to the DNACTMA to increase the electrical conductivity of the biopolymer. The CW absorbance and time-resolved photoluminescence of the resulting DNA-CTMA and DNA-CTMA-PEDOT:PSS were investigated. Both DNA materials have absorbance peaks at ~260 nm and a broad, Stokes shifted, photoluminescence peak around 470nm. The photoluminescence lifetime of the materials was observed to decrease with increasing UV excitation. Specifically, excitation with a high power ultrafast (~150fs) UV (266nm) laser pulse resulted in a drastic decrease in the photoluminescence lifetime decreases after a few minutes. Moreover, the observed decrease was faster in an air ambient than in a nitrogen ambient. This is most likely due to photo-oxidation that degrades the polymer surface resulting in an increase in the non-radiative recombination. In order to investigate the photoconductivity of these two materials, metal-biopolymer-metal (MBM) ultraviolet photodetectors with interdigitated electrodes were fabricated and characterized. The photoresponsivity of these devices was limited by the transport dynamics within the film. The prospects for the use of these materials in optical devices will be discussed

A new capacitive test structure for microwave characterization of biopolymers

A new capacitive test structure, containing a parallel plate capacitor with coplanar waveguide feed lines, was used for microwave characterization of biopolymers for the first time. Microwave dielectric properties were obtained for the biopolymers as a function of dc bias and temperature by performing on-wafer microwave measurements. Dielectric tunability was observed with applied dc bias in the biopolymers tested

The Effects of Printed Lattice Cell Structure Superstrates on Printed Patch Antennas

This work demonstrates a fully printed patch antenna consisting of a three‐dimensional (3D) printed Ultem 9085 substrate and a 3D printed body‐centered cubic lattice cell structure (LCS) superstrate made of Verowhite Plus. The radiating patch was fabricated by manual screen‐printing method using commercially available silver pastes. The superstrate was affixed to the top of the patch to mitigate shock‐induced damage to the patch. The antenna, which operates close to 5 GHz (an alternative frequency band to 2.4 GHz for data link applications) was designed as a test platform to quantify the effects of a printed superstrate on the resonant frequency and bandwidth. The addition of the superstrate shifted the resonant frequency by 0.1 GHz; and while this is not insignificant it still provides a promising strategy for adding vibration mitigation to radio frequency (RF) structures. Further, it was used to assess a less computationally expensive scheme for modeling of RF antennas involving cellular structures. In this scheme, the LCS superstrate is treated as a solid with dielectric properties that resemble that of a porous medium. Comparisons of measured and simulated S11 before and after adding the LCS superstrate revealed that the scheme yields results that are in good agreement with the experiment. Results from this work can provide guidance in the fabrication of low‐cost fully printed patch antennas with LCS superstrate for specific frequency application

The Effects of Printed Lattice Cell Structure Superstrates on Printed Patch Antennas

This work demonstrates a fully printed patch antenna consisting of a three‐dimensional (3D) printed Ultem 9085 substrate and a 3D printed body‐centered cubic lattice cell structure (LCS) superstrate made of Verowhite Plus. The radiating patch was fabricated by manual screen‐printing method using commercially available silver pastes. The superstrate was affixed to the top of the patch to mitigate shock‐induced damage to the patch. The antenna, which operates close to 5 GHz (an alternative frequency band to 2.4 GHz for data link applications) was designed as a test platform to quantify the effects of a printed superstrate on the resonant frequency and bandwidth. The addition of the superstrate shifted the resonant frequency by 0.1 GHz; and while this is not insignificant it still provides a promising strategy for adding vibration mitigation to radio frequency (RF) structures. Further, it was used to assess a less computationally expensive scheme for modeling of RF antennas involving cellular structures. In this scheme, the LCS superstrate is treated as a solid with dielectric properties that resemble that of a porous medium. Comparisons of measured and simulated S11 before and after adding the LCS superstrate revealed that the scheme yields results that are in good agreement with the experiment. Results from this work can provide guidance in the fabrication of low‐cost fully printed patch antennas with LCS superstrate for specific frequency application

Effect Of External Electrical Stimuli on DNA-Based Biopolymers

Biopolymers, such as deoxyribonucleic acid-hexadecyltrimethyl ammonium chloride (DNA-CTMA) and bovine serum albumin-polyvinyl alcohol (BSA-PVA), were studied using a novel capacitive test structure. A variety of external electrical stimuli were applied, including a low frequency alternating current signal and a rf/microwave frequency signal combined with a DC bias. The dynamic responses of the DNA-based biopolymer to the external stimuli are presented in this paper. The electrical transport measurements support the space-charge-limited conduction and the low frequency capacitance–voltage (CV) measurements showed large depletion layer capacitance at the Au–biopolymer interface, at 20 Hz, and the capacitance approaching bulk values at 1 MHz. Electric force microscopy (EFM) was utilized for visualization of charge dynamics and to examine the effect of DC bias combined with an AC signal. Ionic charges in the DNA-CTMA system seem to be responsible for the dynamic response to the various external electrical stimuli

Altered Network Topology in Patients with Primary Brain Tumors After Fractionated Radiotherapy

Radiation therapy (RT) is a critical treatment modality for patients with brain tumors, although it can cause adverse effects. Recent data suggest that brain RT is associated with dose-dependent cortical atrophy, which could disrupt neocortical networks. This study examines whether brain RT affects structural network properties in brain tumor patients. We applied graph theory to MRI-derived cortical thickness estimates of 54 brain tumor patients before and after RT. Cortical surfaces were parcellated into 68 regions and correlation matrices were created for patients pre- and post-RT. Significant changes in graph network properties were tested using nonparametric permutation tests. Linear regressions were conducted to measure the association between dose and changes in nodal network connectivity. Increases in transitivity, modularity, and global efficiency (n = 54, p < 0.0001) were all observed in patients post-RT. Decreases in local efficiency (n = 54, p = 0.007) and clustering coefficient (n = 54, p = 0.005) were seen in regions receiving higher RT doses, including the inferior parietal lobule and rostral anterior cingulate. These findings demonstrate alterations in global and local network topology following RT, characterized by increased segregation of brain regions critical to cognition. These pathological network changes may contribute to the late delayed cognitive impairments observed in many patients following brain RT

Altered Network Topology in Patients with Primary Brain Tumors After Fractionated Radiotherapy

Radiation therapy (RT) is a critical treatment modality for patients with brain tumors, although it can cause adverse effects. Recent data suggest that brain RT is associated with dose-dependent cortical atrophy, which could disrupt neocortical networks. This study examines whether brain RT affects structural network properties in brain tumor patients. We applied graph theory to MRI-derived cortical thickness estimates of 54 brain tumor patients before and after RT. Cortical surfaces were parcellated into 68 regions and correlation matrices were created for patients pre- and post-RT. Significant changes in graph network properties were tested using nonparametric permutation tests. Linear regressions were conducted to measure the association between dose and changes in nodal network connectivity. Increases in transitivity, modularity, and global efficiency (n = 54, p < 0.0001) were all observed in patients post-RT. Decreases in local efficiency (n = 54, p = 0.007) and clustering coefficient (n = 54, p = 0.005) were seen in regions receiving higher RT doses, including the inferior parietal lobule and rostral anterior cingulate. These findings demonstrate alterations in global and local network topology following RT, characterized by increased segregation of brain regions critical to cognition. These pathological network changes may contribute to the late delayed cognitive impairments observed in many patients following brain RT