Hypersensitivity of BRCA1 heterozygote lymphoblastoid cells to gamma radiation and PARP inhibitors

This article is made available through the Brunel Open Access Publishing Fund. Copyright @ 2013 Bourton EC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PARP inhibitors can be used to induce synthetic lethality in cells with bi-allelic BRCA1 and BRCA2 mutations. However the effect of PARP inhibitors in combination with radiation on cells with mono-allelic mutations of BRCA1 and BRCA2 is unknown. We have examined the cell survival response of lymphoblastoid cells derived from normal individuals and those derived from carriers of BRCA1 and BRCA2 mutations, following exposure to ionising radiation and the PARP inhibitor Olaparib. Two lymphoblastoid cell lines from normal individuals and three with mono-allelic mutations in BRCA1 and BRCA2 were exposed to increasing doses of gamma radiation either alone or in combination with 5 μM Olaparib. Cell survival was measured using the MTT assay. Exposure to increasing doses of gamma radiation caused a reduction in cell survival of all cell types. The combined exposure to gamma radiation and 5 μM Olaparib did not enhance cell kill in normal or BRCA2 heterozygote lymphoblastoid cells but significantly enhanced cell kill in cells derived from BRCA1 carriers (P = 0.02). The treatment of cancer patients carrying mutations in the BRCA1 gene with radiotherapy and the PARP inhibitor Olaparib may significantly enhance radiation induced normal tissue toxicity in these patients.Vidal Sassoon Foundation of America and “The Balls to Cancer” Charity, Coventry, U

Understanding and utilization of Thematic Mapper and other remotely sensed data for vegetation monitoring

The TM Tasseled Cap transformation, which provides both a 50% reduction in data volume with little or no loss of important information and spectral features with direct physical association, is presented and discussed. Using both simulated and actual TM data, some important characteristics of vegetation and soils in this feature space are described, as are the effects of solar elevation angle and atmospheric haze. A preliminary spectral haze diagnostic feature, based on only simulated data, is also examined. The characteristics of the TM thermal band are discussed, as is a demonstration of the use of TM data in energy balance studies. Some characteristics of AVHRR data are described, as are the sensitivities to scene content of several LANDSAT-MSS preprocessing techniques

Constraining uncertainty in aerosol direct forcing

The uncertainty in present-day anthropogenic forcing is dominated by uncertainty in the strength of the contribution from aerosol. Much of the uncertainty in the direct aerosol forcing can be attributed to uncertainty in the anthropogenic fraction of aerosol in the present-day atmosphere, due to a lack of historical observations. Here we present a robust relationship between total present-day aerosol optical depth and the anthropogenic contribution across three multi-model ensembles and a large single-model perturbed parameter ensemble. Using observations of aerosol optical depth, we determine a reduced likely range of the anthropogenic component and hence a reduced uncertainty in the direct forcing of aerosol

Structure, magnetic and transport properties of Ti-substituted La0.7Sr0.3MnO3

Ti-substituted perovskites, La0.7Sr0.3Mn1-xTixO3, with x between 0 to 0.20, were investigated by neutron diffraction, magnetization, electric resistivity, and magnetoresistance (MR) measurements. All samples show a rhombohedral structure (space group R3c) from 10 K to room temperature. At room temperature, the cell parameters a, c and the unit cell volume increase with increasing Ti content. However, at 10 K, the cell parameter a has a maximum value for x = 0.10, and decreases for x greater than 0.10, while the unit cell volume remains nearly constant for x greater than 0.10. The average (Mn,Ti)-O bond length increases up to x=0.15, and the (Mn,Ti)-O-(Mn,Ti) bond angle decreases with increasing Ti content to its minimum value at x=0.15 at room temperature. Below the Curie temperature T_C, the resistance exhibits metallic behavior for the x _ 0.05 samples. A metal (semiconductor) to insulator transition is observed for the x_ 0.10 samples. A peak in resistivity appears below T_C for all samples, and shifts to a lower temperature as x increases. The substitution of Mn by Ti decreases the 2p-3d hybridization between O and Mn ions, reduces the bandwidth W, and increases the electron-phonon coupling. Therefore, the TC shifts to a lower temperature and the resistivity increases with increasing Ti content. A field-induced shift of the resistivity maximum occurs at x less than or equal to 0.10. The maximum MR effect is about 70% for La0.7Sr0.3Mn0.8Ti0.2O3. The separation of TC and the resistivity maximum temperature Tmax enhances the MR effect in these compounds due to the weak coupling between the magnetic ordering and the resistivity as compared with La0.7Sr0.3MnO3.Comment: zip fil

Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis

Copyright @ 2012 Nature Publishing GroupThis article has been made available through the Brunel Open Access Publishing Fund.Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.This work was supported in part by The Vidal Sassoon Foundation USA. This article is made available through the Brunel Open Access Publishing Fund

Paedophiles in the community: inter-agency conflict, news leaks and the local press

This article explores the leaking of confidential information about secret Home Office plans to house convicted paedophiles within a local community (albeit inside a prison). It argues that a politics of paedophilia has emerged in which inter-agency consensus on the issue of ‘what to do’ with high-profile sex offenders has broken down. Accordingly, the article situates newspaper ‘outing’ of paedophiles in the community in relation to vigilante journalism and leaked information from official agencies. The article then presents research findings from a case study of news events set in train following a whistle-blowing reaction by Prison Officers’ Association officials to Home Office plans. Drawing from a corpus of 10 interviews with journalists and key protagonists in the story, the article discusses both the dynamics of whistle blowing about paedophiles and also what happens after the whistle has blown

Stress corrosion in titanium alloys and other metallic materials

Multiple physical and chemical techniques including mass spectroscopy, atomic absorption spectroscopy, gas chromatography, electron microscopy, optical microscopy, electronic spectroscopy for chemical analysis (ESCA), infrared spectroscopy, nuclear magnetic resonance (NMR), X-ray analysis, conductivity, and isotopic labeling were used in investigating the atomic interactions between organic environments and titanium and titanium oxide surfaces. Key anhydrous environments studied included alcohols, which contain hydrogen; carbon tetrachloride, which does not contain hydrogen; and mixtures of alcohols and halocarbons. Effects of dissolved salts in alcohols were also studied. This program emphasized experiments designed to delineate the conditions necessary rather than sufficient for initiation processes and for propagation processes in Ti SCC

Strong coupling theory for driven tunneling and vibrational relaxation

We investigate on a unified basis tunneling and vibrational relaxation in driven dissipative multistable systems described by their N lowest lying unperturbed levels. By use of the discrete variable representation we derive a set of coupled non-Markovian master equations. We present analytical treatments that describe the dynamics in the regime of strong system-bath coupling. Our findings are corroborated by ``ab-initio'' real-time path integral calculations.Comment: 4 LaTeX pages including 3 figure

Fluorescence decay in aperiodic Frenkel lattices

We study motion and capture of excitons in self-similar linear systems in which interstitial traps are arranged according to an aperiodic sequence, focusing our attention on Fibonacci and Thue-Morse systems as canonical examples. The decay of the fluorescence intensity following a broadband pulse excitation is evaluated by solving the microscopic equations of motion of the Frenkel exciton problem. We find that the average decay is exponential and depends only on the concentration of traps and the trapping rate. In addition, we observe small-amplitude oscillations coming from the coupling between the low-lying mode and a few high-lying modes through the topology of the lattice. These oscillations are characteristic of each particular arrangement of traps and they are directly related to the Fourier transform of the underlying lattice. Our predictions can be then used to determine experimentally the ordering of traps.Comment: REVTeX 3.0 + 3PostScript Figures + epsf.sty (uuencoded). To appear in Physical Review