14,225 research outputs found
Dysfunctional telomeres in primary cells from Fanconi anemia FANCD2 patients
© 2012 Joksic et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Fanconi anemia (FA) is characterized by sensitivity to DNA cross-linking agents, mild cellular, and marked clinical radio sensitivity. In this study we investigated telomeric abnormalities of non-immortalized primary cells (lymphocytes and fibroblasts) derived from FA patients of the FA-D2 complementation group, which provides a more accurate physiological assessment than is possible with transformed cells or animal models. Results: We analyzed telomere length, telomere dysfunction-induced foci (TIFs), sister chromatid exchanges (SCE), telomere sister chromatid exchanges (T-SCE), apoptosis and expression of shelterin components TRF1 and TRF2. FANCD2 lymphocytes exhibited multiple types of telomeric abnormalities, including premature telomere shortening, increase in telomeric recombination and aberrant telomeric structures ranging from fragile to long-string extended telomeres. The baseline incidence of SCE in FANCD2 lymphocytes was reduced when compared to control, but in response to diepoxybutane (DEB) the 2-fold higher rate of SCE was observed. In contrast, control lymphocytes showed decreased SCE incidence in response to DEB treatment. FANCD2 fibroblasts revealed a high percentage of TIFs, decreased expression of TRF1 and invariable expression of TRF2. The percentage of TIFs inversely correlated with telomere length, emphasizing that telomere shortening is the major reason for the loss of telomere capping function. Upon irradiation, a significant decrease of TIFs was observed at all recovery times. Surprisingly, a considerable percentage of TIF positive cells disappeared at the same time when incidence of γ-H2AX foci was maximal. Both FANCD2 leucocytes and fibroblasts appeared to die spontaneously at higher rate than control. This trend was more evident upon irradiation; the percentage of leucocytes underwent apoptosis was 2.59- fold higher than that in control, while fibroblasts exhibited a 2- h delay before entering apoptosis. Conclusion:
The results of our study showed that primary cells originating from FA-D2 patients display shorten telomeres, elevated incidence of T-SCEs and high frequency of TIFs. Disappearance of TIFs in early response to irradiation represent distinctive feature of FANCD2 cells that should be examined further.This article is made available through the Brunel Open Access Publishing Fund. This work was supported by the Ministry of Education and Science of the Republic of Serbia (Project No.173046)
A generalised formulation for computing the microbuckling load in periodic layered materials
Acknowledgments The financial support of the part of this research by The Royal Society, The Royal Academy of Engineering and The Carnegie Trust for the Universities of Scotland is gratefully acknowledged.Peer reviewedPostprin
What Belongs Where? Variable Selection for Zero-Inflated Count Models with an Application to the Demand for Health Care
This paper develops stochastic search variable selection (SSVS) for zero-inflated count models which are commonly used in health economics. This allows for either model averaging or model selection in situations with many potential regressors. The proposed techniques are applied to a data set from Germany considering the demand for health care. A package for the free statistical software environment R is provided.Bayesian, model selection, model averaging, count data, zero-inflation, demand for health care
Random telegraph signals in proton irradiated CCDs and APS
Random telegraph dark signal fluctuations have been studied in two types of CCD and two types of CMOS active pixel sensor after proton irradiation at 1.5, 10 and 60 MeV. Time constants and activation energies were very similar, indicating a similar defect type. A large fraction of the defects are multi- rather than 2-level, suggesting a mechanism related to defect clusters being formed from initial single proton events
JoXSZ: Joint X-SZ fitting code for galaxy clusters
The thermal Sunyaev-Zeldovich (SZ) effect and the X-ray emission offer
separate and highly complementary probes of the thermodynamics of the
intracluster medium. We present JoXSZ, the first publicly available code
designed to jointly fit SZ and X-ray data coming from various instruments to
derive the thermodynamic profiles of galaxy clusters. JoXSZ follows a fully
Bayesian forward-modelling approach, accounts for the SZ calibration
uncertainty and X-ray background level systematic. It improves upon most
state-of-the-art, and not publicly available, analyses because it adopts the
correct Poisson-Gauss expression for the joint likelihood, makes full use of
the information contained in the observations, even in the case of missing
values within the datasets, has a more inclusive error budget, and adopts a
consistent temperature across the various parts of the code, allowing for
differences between X-ray and SZ gas mass weighted temperatures when required
by the user. JoXSZ accounts for beam smearing and data analysis transfer
function, accounts for the temperature and metallicity dependencies of the SZ
and X-ray conversion factors, adopts flexible parametrization for the
thermodynamic profiles, and on user request allows either adopting or relaxing
the assumption of hydrostatic equilibrium (HE). When HE holds, JoXSZ uses a
physical (positive) prior on the radial derivative of the enclosed mass and
derives the mass profile and overdensity radii . For these reasons,
JoXSZ goes beyond simple SZ and electron density fits. We illustrate the use of
JoXSZ by combining Chandra and NIKA data on the high-redshift cluster CL
J1226.9+3332. The code is written in Python, it is fully documented and the
users are free to customize their analysis in accordance with their needs and
requirements. JoXSZ is publicly available on GitHub.Comment: 11 pages, 9 figures, accepted for publication in Astronomy and
Astrophysics. Code available on GitHub at https://github.com/fcastagna/JoXSZ.
v2 updated with language editin
- …