Differential TERT promoter methylation and response to 5-aza-2'-deoxycytidine in acute myeloid leukemia cell lines:TERT expression, telomerase activity, telomere length, and cell death

The catalytic subunit of human telomerase (TERT) is highly expressed in cancer cells, and correlates with complex cytogenetics and disease severity in acute myeloid leukemia (AML). The TERT promoter is situated within a large CpG island, suggesting that expression is methylation-sensitive. Studies suggest a correlation between hypermethylation and TERT overexpression. We investigated the relationship between TERT promoter methylation and expression and telomerase activity in human leukemia and lymphoma cell lines. DAC-induced demethylation and cell death were observed in all three cell lines, as well as telomere shortening in HL-60 cells. DAC treatment reduced TERT expression and telomerase activity in OCI/AML3 and HL-60 cells, but not in U937 cells. Control U937 cells expressed lower levels of TERT mRNA, carried a highly methylated TERT core promoter, and proved more resistant to DAC-induced repression of TERT expression and cell death. AML patients had significantly lower methylation levels at several CpGs than "well elderly" individuals. This study, the first to investigate the relationship between TERT methylation and telomerase activity in leukemia cells, demonstrated a differential methylation pattern and response to DAC in three AML cell lines. We suggest that, although DAC treatment reduces TERT expression and telomerase activity, this is unlikely to occur via direct demethylation of the TERT promoter. However, further investigations on the regions spanning CpGs 7-12 and 14-16 may reveal valuable information regarding transcriptional regulation of TERT.

Premiere of "Spaced Images with Noise and Lines" Performance at the Joinery, Dublin, at at Spatial Music Collective concert. Authors: Lyon, E. Keywords: (Spatial Audio, Electroacoustic Music, Computer Music, Algorithmic Music) Publication date: 07 Oct 2011

Performance at the Joinery, Dublin, at at Spatial Music Collective concert

In-vitro investigation of out-of-field cell survival following the delivery of conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans

The aim of this work is to determine the out-of-field survival of cells irradiated with either the primary field or scattered radiation in the presence and absence of intercellular communication following delivery of conformal, IMRT and VMAT treatment plans. Single beam, conformal, IMRT and VMAT plans were created to deliver 3 Gy to half the area of a T80 flask containing either DU-145 or AGO-1522 cells allowing intercellular communication between the in-and out-of-field cell populations. The same plans were delivered to a similar custom made phantom used to hold two T25 culture flasks, one flask in-field and one out-of-field to allow comparison of cell survival responses when intercellular communication is physically inhibited. Plans were created for the delivery of 8 Gy to the more radio-resistant DU-145 cells only in the presence and absence of intercellular communication. Cell survival was determined by clonogenic assay. In both cell lines, the out-of-field survival was not statistically different between delivery techniques for either cell line or dose. There was however, a statistically significant difference between survival out-of-field when intercellular communication was intact (single T80 culture flask) or inhibited (multiple T25 culture flasks) to in-field for all plans. No statistically significant difference was observed in-field with or without cellular communication to out-of-field for all plans. These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields when cellular communication between differentially irradiated cell populations is present. This data is further evidence that refinement of existing radiobiological models to include indirect cell killing effects is required.

Detection of magnetic dipole lines of Fe XII in the ultraviolet spectrum of the dwarf star ε Eri

We report observations of the dwarf star e Eri (K2V) made with the Space Telescope Imaging Spectrograph (STIS) on the Hubble Space Telescope. The high sensitivity of the STIS instrument has allowed us to detect the magnetic dipole transitions of Fe XII at 1242.00 and 1349 38 Å for the first time in a star other than the Sun. The width of the stronger line at 1242.00 Å has also been measured; such measurements are not possible for the permitted lines of Fe XII in the extreme-ultraviolet. To within the accuracy of the measurements the N v and the Fe XII lines occur at their rest wavelengths. Electron densities and linewidths have been measured from other transition region lines. Together, these can be used to investigate the non-thermal energy flux in the lower and upper transition regions, which is useful in constraining possible heating processes. The Fe XII lines are also present in archival STIS spectra of other G/K-type dwarfs.

Modelling the H Lyman lines in evolved late-type stars

The importance of partial redistribution (PRD) in the modelling of the Lyman a and Lyman ß emission lines of hydrogen in stellar atmospheres is examined using simple atmospheric models of a range of late-type stars. These models represent the subgiant Procyon (F5 IV-V), and the two giants ß Gem (K0 III) and a Tau (K5 III). These stars are selected to span a wide range of surface gravities: 1.25 <log g <4.00. The calculations are performed using the computer code MULTI with the modifications made by Hubeny & Lites. It is found that PRD effects are highly significant, both in the direct prediction of the Lyman line profiles and in the application of hydrostatic equilibrium to calculate the atmospheric electron density in static atmospheric models.

Distributed passive intermodulation generation in coplanar waveguide transmission lines

A phenomenology of distributed passive intermodulation generation in coplanar waveguide transmission line is presented. The theoretical analysis is based upon the generalised nonlinear transmission line model, which accounts for the coupling of two propagating modes. The case of weak substrate nonlinearity is considered and the model is given qualitative verification through the mapping of passive intermodulation products generated in coplanar waveguide fabricated on a commercial laminate. Implications for future research are discussed. © 2012 IEEE.