The PHLPP2 phosphatase is a druggable driver of prostate cancer progression

Metastatic prostate cancer commonly presents with targeted, bi-allelic mutations of the PTEN and TP53 tumor suppressor genes. In contrast, however, most candidate tumor suppressors are part of large recurrent hemizygous deletions, such as the common chromosome 16q deletion, which involves the AKT-suppressing phosphatase PHLPP2. Using RapidCaP, a genetically engineered mouse model of Pten/Trp53 mutant metastatic prostate cancer, we found that complete loss of Phlpp2 paradoxically blocks prostate tumor growth and disease progression. Surprisingly, we find that Phlpp2 is essential for supporting Myc, a key driver of lethal prostate cancer. Phlpp2 dephosphorylates threonine-58 of Myc, which renders it a limiting positive regulator of Myc stability. Furthermore, we show that small-molecule inhibitors of PHLPP2 can suppress MYC and kill PTEN mutant cells. Our findings reveal that the frequent hemizygous deletions on chromosome 16q present a druggable vulnerability for targeting MYC protein through PHLPP2 phosphatase inhibitors

2D Thermoluminescence imaging of dielectric surface long term charge memory of plasma surface interaction in DBD discharges

The charge trapping effect due to the exposure of alumina surfaces to plasma has been studied in a volume dielectric barrier discharge (DBD) in Ar and He noble gases. The long lasting charge trapping of alumina dielectric plates, used as barriers in DBDs, is evidenced by an ex situ thermoluminescence (TL) experiment performed with a standard and a custom two-dimensional (2D)-TL apparatus. The spatial density of trapped surface charges is found to be strongly correlated to the plasma morphology, and the surface spatial memory lasted for several minutes to hours after plasma exposure. In the case of Ar, the plasma channel impact signature on the surface shows a higher equivalent radiation dose with respect to the surface plasma wave and the post-discharge species signature. As a consequence, for the development of discharges, inside the dielectric surface the availability of lower energy trapped electrons is larger in the first region of plasma impact. The reported spatial memory increases the likelihood of the occurrence of plasma filaments in the same position in different runs. In He plasmas, the dielectric barrier shows an almost uniform distribution of trapped charges, meaning that there is no preferred region for the development of the discharge. In all cases a slight asymmetry was shown in the direction of the gas flow. This can be interpreted as being due to the long-living species moving in the direction of the gas flow, corresponding with the TL side experiment on the sample exposed to the plasma afterglow. The maximum values and the integral of the 2D-TL images showed a linear relation with the total charge per ac cycle, corresponding with findings for the TL glow curve. In conclusion, 2D-TL images allow the retrieval of information regarding the plasma surface interaction such as the plasma morphology, trap sites and their activation temperature

Parametric study of plasma-mediated thermoluminescence produced by Al2O3 sub-micron powders

Sub-micron Al2O3 powders with a surface activated by dielectric barrier discharge exhibit improved performance in wet deposition of ceramic layers. In addressing the possible mechanisms responsible for the observed improvement, a comprehensive thermoluminescence (TL) study of plasma-activated powders was performed. TL offers the unique possibility of exploring the population of intrinsic electrons/holes in the charge trapping states. This study covers a wide range of experimental conditions affecting the TL of powders: treatment time, plasma working gas composition, change of discharge configuration, step-annealing of powder, exposure to laser irradiation and aging time. Deconvoluted TL spectra were followed for the changes in their relative contributions. The TL spectra of all tested gases (air, Ar, N2 and 5% He in N2) consist of the well-known main dosimetric peak at 450 K and a peak of similar magnitude at higher temperatures, centered between 700 and 800 K depending on the working gas used. N2 plasma treatment gave rise to a new specific TL peak at 510 K, which exhibited several peculiarities. Initial thermal annealing of Al2O3 powders led to its significant amplification (unlike the other peaks); the peak was insensitive to optical bleaching, and it exhibited slow gradual growth during the long-term aging test. Besides its relevance to the ceramic processing studies, a comprehensive set of data is presented that provides a useful and unconventional view on plasma-mediated material changes

Early Altered Cells Health Status Detection via Label Free Impedance and Broadband dielectric Spectroscopy

Human cells are able to respond to applied electrical signals and their response is different according to cell health status. In this framework, the electrical bio-impedance can be sensitive tools to monitor cellular health status in addition to other commonly adopted biological methods. Here we show that in vitro cellular lines affected by inflammatory processes or outside insult can be identified by using impedance and broadband dielectric spectroscopy analysis. The analysis of specific parameters of the electrical response evidences modification in the cells compartments. The features of the cell electrical response allow to discriminate between the different processes involved

Surface chemistry and morphology effects on optoelectronic transport at metal/nanostructured silicon/silicon structures

This work enlighten on the modification of the electrical and optoelectronic properties at metal/silicon interface, where the silicon surface is nanostructured by single step mask-less CF4 plasma in reactive ion etching mode. The electrical transport across metal/nanotextured silicon/silicon structure has been correlated with morphological variations of surface topological features and chemistry. The results evidence that such nanostructures enhance the photovoltaic behavior and affect electrical and optoelectronic transport to a different extent, depending not only on surface texturing but also on surface chemistry. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4710989

Thermoluminescence study of the trapped charge at an alumina surface electrode in different dielectric barrier discharge regimes

In this study, the charge trapping effect in alumina dielectric surfaces has been deeply investigated by means of a dedicated dielectric barrier discharge apparatus in different discharge regimes and gas mixtures. This work further validates our previous findings in the case of air discharges in a filamentary regime. Long lasting charge trapping has been evidenced by ex situ thermoluminescence characterizations of alumina dielectric barrier plates exposed to a plasma. The density of trapped surface charges was found to be higher in the glow discharge with respect to pseudo-glow and filamentary regimes, and for all regimes the minimum trap activation temperature was 390K and the trap energy was less than or around 1 eV. This implies that in the case of glow discharges a higher reservoir of electrons is present. Also, the effect was found to persist for several days after running the discharge

Keratinocyte cellular damage induced by pesticide doses below the cytotoxic level evidenced by electrical impedance and broadband dielectric spectroscopy

The cellular response of a normal human keratinocyte cell line exposed to non-cytotoxic doses of a deltamethrin-based pesticide was investigated by means of two different electrical impedance data spectroscopy approaches: Nyquist plot and broadband dielectric spectroscopy. The measurements have shown that the membrane capacity increases with pesticide concentration and this facilitates the electric current through cell membranes. Furthermore, the impedance of the extracellular matrix also increases with pesticide concentration, thus reducing the electric current outside the cell. Dielectric permittivity changes in the cellular samples at frequencies larger than 100 Hz. Fluorescence (FL) measurements emphasized an increase in neutral membrane lipids as a consequence of the pesticide exposure. Comparison of FL response of pesticide exposed cells with the control ones showed a time increase in the emission intensity, suggesting the existence of a membrane lipid response aimed at repairing the cell damage due to pesticide exposure. Therefore, both spectroscopic techniques have been demonstrated as potential means to investigate the response to cell stress and damage. This opens up new possibilities in the early diagnosis of cellular modifications related to the pesticide exposure of cells