Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic, chemoresistant malignancy and is characterized by a dense, desmoplastic stroma that modulates PDAC progression. Here, we visualized transient manipulation of focal adhesion kinase (FAK), which integrates bidirectional cell-environment signaling, using intravital fluorescence lifetime imaging microscopy of the FAK-based Förster resonance energy transfer biosensor in mouse and patient-derived PDAC models. Parallel real-time quantification of the FUCCI cell cycle reporter guided us to improve PDAC response to standard-of-care chemotherapy at primary and secondary sites. Critically, micropatterned pillar plates and stiffness-tunable matrices were used to pinpoint the contribution of environmental cues to chemosensitization, while fluid flow–induced shear stress assessment, patient-derived matrices, and personalized in vivo models allowed us to deconstruct how FAK inhibition can reduce PDAC spread. Last, stratification of PDAC patient samples via Merlin status revealed a patient subset with poor prognosis that are likely to respond to FAK priming before chemotherapy.Kendelle J. Murphy ... Michael S. Samuel ... et al. [Australian Pancreatic Genome Initiative (APGI), Australian Pancreatic Cancer Matrix Atlas (APMA)

BV solutions of a singular diffusion equation

10.1002/mana.200310047Mathematische Nachrichten25392-10

Free-boundary problem for a singular diffusion equation

10.1006/jmaa.2001.7729Journal of Mathematical Analysis and Applications2652414-42

Free-standing ZnO-CuO composite nanowire array films and their gas sensing properties

A modified hydrothermal method was developed to synthesize ZnO-CuO composite nanostructures. A free-standing film made of ZnO-CuO nanostructures was assembled on the surface of the hydrothermal solution with a smooth surface on one side and a spherical surface on the other side. The structure, growth mechanism and the optical properties of the composite nanostructures were studied. Structural characterizations indicate that the composite nanostructure mainly consisted of two single-crystal phases of CuO and ZnO. The sensitivity for CO gas detection was significantly improved for the composite CuO-ZnO nanostructure film. This method offers a possible route for the fabrication of free-standing nanostructure films of different functional composite oxides. © 2011 IOP Publishing Ltd

18-GHz 3.65-W/mm enhancement-mode AlGaN/GaN HFET using fluorine plasma ion implantation

Enhancement-mode (E-mode) AlGaN/GaN heterojunction field effect transistors (HFETs) with a nominal gate length of 0.35 μm are fabricated on a SiC substrate by fluorine plasma ion implantation without the use of gate recess. The threshold voltage is measured to be +0.2 V by linear extrapolation from the transfer characteristics. The E-mode device exhibits a saturation drain current density of 735 mA/mm at a gate bias of 4 V, a peak transconductance of 269 mS/mm, a current-gain cutoff frequency f_T of 39 GHz, and a maximum oscillation frequency f_max of 91 GHz. At 18 GHz, the fabricated E-mode device exhibits a maximum output power density of 3.65 W/mm, a linear gain of 11.6 dB, and a peak power-added efficiency of 42%. This is the first report of the large-signal performance of AlGaN/GaN E-mode HFETs in the Ku-band. © 2006 IEEE