The effect of chemotherapeutic agents on telomere length maintenance in breast cancer cell lines

Copyright @ 2014 the authors. This article is made available through the Brunel Open Access Publishing Fund. It is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Mammalian telomeric DNA consists of tandem repeats of the sequence TTAGGG associated with a specialized set of proteins, known collectively as Shelterin. These telosomal proteins protect the ends of chromosomes against end-to-end fusion and degradation. Short telomeres in breast cancer cells confer telomere dysfunction and this can be related to Shelterin proteins and their level of expression in breast cancer cell lines. This study investigates whether expression of Shelterin and Shelterin-associated proteins are altered, and influence the protection and maintenance of telomeres, in breast cancer cells. 5-aza-2'-deoxycytidine (5-aza-CdR) and trichostatin A (TSA) were used in an attempt to reactivate the expression of silenced genes. Our studies have shown that Shelterin and Shelterin-associated genes were down-regulated in breast cancer cell lines; this may be due to epigenetic modification of DNA as the promoter region of POT1 was found to be partially methylated. Shelterin genes expression was up-regulated upon treatment of 21NT breast cancer cells with 5-aza-CdR and TSA. The telomere length of treated 21NT cells was measured by q-PCR showed an increase in telomere length at different time points. Our studies have shown that down-regulation of Shelterin genes is partially due to methylation in some epithelial breast cancer cell lines. Removal of epigenetic silencing results in up-regulation of Shelterin and Shelterin-associated genes which can then lead to telomere length elongation and stability

Ultraluminous X-ray Sources forming in low metallicity natal environments

In the last few years multiwavelength observations have boosted our understanding of Ultraluminous X-ray Sources (ULXs). Yet, the most fundamental questions on ULXs still remain to be definitively answered: do they contain stellar or intermediate mass black holes? How do they form? We investigate the possibility that the black holes hosted in ULXs originate from massive (40-120 $M_\odot$) stars in low metallicity natal environments. Such black holes have a typical mass in the range $\sim 30-90 M_\odot$ and may account for the properties of bright (above $\sim 10^{40}$ erg s$^{-1}$) ULXs. More than $\sim 10^5$ massive black holes might have been generated in this way in the metal poor Cartwheel galaxy during the last $10^7$ years and might power most of the ULXs observed in it. Support to our interpretation comes from NGC 1313 X-2, the first ULX with a tentative identification of the orbital period in the optical band, for which binary evolution calculations show that the system is most likely made by a massive donor dumping matter on a $50-100 M_\odot$ black hole.Comment: 4 pages. To appear in the Proceedings of the Conference "X-Ray Astronomy 2009: Present Status, Multiwavelength Approach and Future Perspectives", Bologna, Italy, September 2009, Eds. A. Comastri, M. Cappi, L. Angelini, 2010 AIP (in press)

Mentoring to reduce antisocial behaviour in childhood

The effects of social interventions need to be examined in real life situations as well as studie

Nutritional support for head-injured patients

Copyright John Wiley & Sons. This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2004, Issue 3. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Perel, P. , Yanagawa, T. , Bunn, F. , Roberts, I. , Wentz, R. and Pierro, A. Nutritional support for head-injured patients. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD001530. DOI: 10.1002/14651858.CD001530.pub2Background: Head injury increases the body's metabolic responses, and therefore nutritional demands. Provision of an adequate supply of nutrients is associated with improved outcome. The best route for administering nutrition (parenterally (TPN) or enterally (EN)), and the best timing of administration (for example, early versus late) of nutrients needs to be established. Objectives: To quantify the effect on mortality and morbidity of alternative strategies of providing nutritional support following head injury. Search strategy: Trials were identified by computerised searches of the Cochrane Injuries Group specialised register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, National Research Register, Web of Science and other electronic trials registers. Reference lists of trials and review articles were checked. The searches were last updated in July 2006. Selection criteria: Randomised controlled trials of timing or route of nutritional support following acute traumatic brain injury. Data collection and analysis: Two authors independently abstracted data and assessed trial quality. Information was collected on death, disability, and incidence of infection. If trial quality was unclear, or if there were missing outcome data, trialists were contacted in an attempt to get further information. Main results: A total of 11 trials were included. Seven trials addressed the timing of support (early versus delayed), data on mortality were obtained for all seven trials (284 participants). The relative risk (RR) for death with early nutritional support was 0.67 (95% CI 0.41 to 1.07). Data on disability were available for three trials. The RR for death or disability at the end of follow-up was 0.75 (95% CI 0.50 to 1.11). Seven trials compared parenteral versus enteral nutrition. Because early support often involves parenteral nutrition, three of the trials are also included in the previous analyses. Five trials (207 participants) reported mortality. The RR for mortality at the end of follow-up period was 0.66 (0.41 to 1.07). Two trials provided data on death and disability. The RR was 0.69 (95% Cl 0.40 to 1.19). One trial compared gastric versus jejunal enteral nutrition, there were no deaths and the RR was not estimable. Authors' conclusions: This review suggests that early feeding may be associated with a trend towards better outcomes in terms of survival and disability. Further trials are required. These trials should report not only nutritional outcomes but also the effect on death and disability.Peer reviewe

Dyson-Schwinger Equations - aspects of the pion

The contemporary use of Dyson-Schwinger equations in hadronic physics is exemplified via applications to the calculation of pseudoscalar meson masses, and inclusive deep inelastic scattering with a determination of the pion's valence-quark distribution function.Comment: 4 pages. Contribution to the Proceedings of ``DPF 2000,'' the Meeting of the Division of Particles and Fields of the American Physical Society, August 9-12, 2000, Department of Physics, the Ohio State University, Columbus, Ohi

The 3D inelastic analysis methods for hot section components

Advanced 3-D inelastic structural/stress analysis methods and solution strategies for more accurate and yet more cost-effective analysis of combustors, turbine blades, and vanes are being developed. The approach is to develop four different theories, one linear and three higher order with increasing complexities including embedded singularities. Progress in each area is reported

The Renal Lymphatics - an Important Fluid Transport System

Study of renal lymph fluid transport syste

A Gaussian process framework for modelling instrumental systematics: application to transmission spectroscopy

Transmission spectroscopy, which consists of measuring the wavelength-dependent absorption of starlight by a planet's atmosphere during a transit, is a powerful probe of atmospheric composition. However, the expected signal is typically orders of magnitude smaller than instrumental systematics, and the results are crucially dependent on the treatment of the latter. In this paper, we propose a new method to infer transit parameters in the presence of systematic noise using Gaussian processes, a technique widely used in the machine learning community for Bayesian regression and classification problems. Our method makes use of auxiliary information about the state of the instrument, but does so in a non-parametric manner, without imposing a specific dependence of the systematics on the instrumental parameters, and naturally allows for the correlated nature of the noise. We give an example application of the method to archival NICMOS transmission spectroscopy of the hot Jupiter HD 189733, which goes some way towards reconciling the controversy surrounding this dataset in the literature. Finally, we provide an appendix giving a general introduction to Gaussian processes for regression, in order to encourage their application to a wider range of problems.Comment: 6 figures, 1 table, accepted for publication in MNRA

New insights into ultraluminous X-ray sources from deep XMM-Newton observations

The controversy over whether ultraluminous X-ray sources (ULXs) contain a new intermediate-mass class of black holes (IMBHs) remains unresolved. We present new analyses of the deepest XMM-Newton observations of ULXs that address their underlying nature. We examine both empirical and physical modelling of the X-ray spectra of a sample of thirteen of the highest quality ULX datasets, and find that there are anomalies in modelling ULXs as accreting IMBHs with properties simply scaled-up from Galactic black holes. Most notably, spectral curvature above 2 keV in several sources implies the presence of an optically-thick, cool corona. We also present a new analysis of a 100 ks observation of Holmberg II X-1, in which a rigorous analysis of the temporal data limits the mass of its black hole to no more than 100 solar masses. We argue that a combination of these results points towards many (though not necessarily all) ULXs containing black holes that are at most a few 10s of solar mass in size.Comment: 5 pages, 2 figures, to appear in the proceedings of "The X-ray Universe 2005", San Lorenzo de El Escorial (Spain), 26-30 September 200