Reduced chromosome aberration complexity in normal human bronchial epithelial cells exposed to low-LET γ-rays and high-LET α-particles

This article is made available through the Brunel Open Access Publishing Fund.Copyright © 2013 The Author(s). Purpose: Cells of the lung are at risk from exposure to low and moderate doses of ionizing radiation from a range of environmental and medical sources. To help assess human health risks from such exposures, a better understanding of the frequency and types of chromosome aberration initially-induced in human lung cell types is required to link initial DNA damage and rearrangements with transmission potential and, to assess how this varies with radiation quality. Materials and methods: We exposed normal human bronchial lung epithelial (NHBE) cells in vitro to 0.5 and 1 Gy low-linear energy transfer (LET) γ-rays and a low fluence of high-LET α-particles and assayed for chromosome aberrations in premature chromosome condensation (PCC) spreads by 24-color multiplex-fluorescence in situ hybridization (M-FISH). Results: Both simple and complex aberrations were induced in a LET and dose-dependent manner; however, the frequency and complexity observed were reduced in comparison to that previously reported in spherical cell types after exposure to comparable doses or fluence of radiation. Approximately 1–2% of all exposed cells were categorized as being capable of transmitting radiation-induced chromosomal damage to future NHBE cell generations, irrespective of dose. Conclusion: One possible mechanistic explanation for this reduced complexity is the differing geometric organization of chromosome territories within ellipsoid nuclei compared to spherical nuclei. This study highlights the need to better understand the role of nuclear organization in the formation of exchange aberrations and, the influence three-dimensional (3D) tissue architecture may have on this in vivo.Department of Health, UK (Contract RRX115)

Altruism and Voluntary Provision of Public Goods

We study how people's predisposition towards altruism, as measured by tools developed by psychologists, affects their behavior in a voluntary contributions public good experiment. Earlier experiments provide evidence against the strong free rider hypothesis; however, contributions to the public good decrease with repetition. We investigate whether a high level of contributions can be sustained in groups of subjects who have been pre-selected on the basis of their altruistic inclinations. In the first stage of the experiment, each subject responds to a psychology questionnaire that measures various dimensions of one's personality. The subjects are then matched in groups according to their altruism scores, and engage in a voluntary contribution game. We consider whether the levels and dynamics of group contributions differ significantly between the groups with altruists and non-altruists. We find that subjects' altruism has a weak but positive effect on group behavior in the public good game.

Altruism and voluntary provision of public goods

We study how people's predisposition towards altruism affects their behavior in a voluntary contributions public good experiment. We investigate whether a high level of contributions can be sustained in groups of subjects who have been pre-selected on the basis of their altruistic inclinations. In the first stage of the experiment, each subject responds to a psychology questionnaire that measures various dimensions of one''s personality. The subjects are then matched in groups according to their altruism scores, and engage in a voluntary contributions game. We consider whether the levels and dynamics of group contributions differ significantly between the groups with altruists and non-altruists. We find that subjects'' altruism has only a weak positive effect on group behavior in the public good game.Altruism

Effect of linear energy transfer (LET) on complexity of alpha-particle-induced chromosome aberrations in human CD34+ cells.

The aim of this study was to assess the relative influence of linear energy transfer (LET) of α-particles on chromosome aberration complexity in the absence of significant other track structure differences. To do this we irradiated human haemopoietic stem cells (CD34+) with The aim of this study was to assess the relative influence of linear energy transfer (LET) of α-particles of various incident LET values (110 - 152 keV/µm, with mean LETs through the cell of 119 – 182 keV/µm) at an equi-fluence of approximately 1 α-particle/cell and assayed for chromosome aberrations by m-FISH. Based on a single harvest time to collect early division mitosis , complex aberrations were observed at comparable frequencies irrespective of incident LET, however when expressed as a proportion of the total exchanges detected, their occurrence was seen to increase with increasing LET. Cycle analysis to predict theoretical DNA double strand break rejoining cycles was also carried out on all complex chromosome aberrations detected. By doing this we found that the majority of complex aberrations are formed in single non-reducible cycles that involve just 2 or 3 different chromosomes and 3 or 4 different breaks. Each non-reducible cycle is suggested to represent ‘an area’ of finite size within the nucleus where double strand break repair occurs. We suggest that local density of damage induced and proximity of independent repair areas within the interphase nucleus determine the complexity of aberration resolved in metaphase. Overall, the most likely outcome of a single nuclear traversal of a single α-particle in CD34+ cells is a single chromosome aberration per damaged cell. As the incident LET of the α-particle increases, the likelihood of this aberration being classed as complex is greater

Floor Mapping: A Novel Method of Integrating Anatomical Structure with Immunological Function

Session - Assessment (Abstract)This free journal suppl. entitled: Special Issue: Abstracts of the 13th Asia Pacific Medical Education Conference (APMEC) ... 2016The Biomedical Common Year 1 occurs prior to admission to the medical programme. Students achieving a grade point average over 6.0 are eligible for an admissions interview. The research question of the study was, “If students have a definite interest in becoming a future doctor in their premedical course, does this relate to their levels of motivation, competitiveness, perceived stress, quality of life and grade attainment?” A total of 1369 students who completed a high stakes biosciences assessment were asked to disclose their grade (converted to a numerical value) and to complete the Motivated Strategies for Learning Questionnaire, a World Health Organisation Quality Of Life (QoL) questionnaire, Perceived Stress Scale, and Revised Competitiveness Index. To explore differences between those students who aimed to be doctors vs those who did not, a binary logistic regression was conducted. Twenty five percent of students participated in the research. Significant predictors of course intention (medicine; other) were academic attainment, perceived stress, and physical and environmental QoL. Post hoc analyses revealed that perceived stress and physical QoL were moderating variables. Students with an intention to become a doctor tend to attain higher grades and have better environmental quality of life scores. This may indicate that students who are admitted into medical school gain higher grades but also likely come from more affluent and well-resourced backgrounds. Physical health problems and perceived stress are likely to moderate the impact of grade achievement, environmental QoL, competition and motivation.link_to_OA_fulltex

Methimazolyl based diptych bicyclo-[3.3.0]-ruthenaboratranes

The reactions of [RuCl(R)(CO)(PPh3)2] (R = CH[double bond, length as m-dash]CHPh, Ph) with Na[H2B(mt)2] (mt = N-methyl-2-mercaptoimidazolyl) transiently provide [Ru(R)(CO)(PPh3){κ3-H,S,S′-H2B(mt)2}] which each evolve to the ruthenaboratrane [Ru(CO)(PPh3)2{κ3-B,S,S′-BH(mt)2}](Ru→B)8. The phosphine ligands may be selectively replaced to provide the complexes [Ru(CO)(L)(PPh3){κ3-B,S,S′-BH(mt)2}] (L = CO, PMe2Ph) and [Ru(CO)L2{κ3-B,S,S′-BH(mt)2}] (L = PMe2Ph, P(OMe)3, L2 = Z-Ph2PCH[double bond, length as m-dash]CHPPh2) with, in each case, retention of the ruthenium–boron dative bond.This work was supported by the Australian Research Council (DP170102695)

Relative proximity of chromosome territories influences chromosome exchange partners in radiation-induced chromosome rearrangements in primary human bronchial epithelial cells

Copyright © 2013 The Authors. This article is made available through the Brunel Open Access Publishing Fund. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.Copyright © 2013 The Authors. It is well established that chromosomes exist in discrete territories (CTs) in interphase and are positioned in a cell-type specific probabilistic manner. The relative localisation of individual CTs within cell nuclei remains poorly understood, yet many cancers are associated with specific chromosome rearrangements and there is good evidence that relative territorial position influences their frequency of exchange. To examine this further, we characterised the complexity of radiation-induced chromosome exchanges in normal human bronchial epithelial (NHBE) cells by M-FISH analysis of PCC spreads and correlated the exchanges induced with their preferred interphase position, as determined by 1/2-colour 2D-FISH analysis, at the time of irradiation. We found that the frequency and complexity of aberrations induced were reduced in ellipsoid NHBE cells in comparison to previous observations in spherical cells, consistent with aberration complexity being dependent upon the number and proximity of damaged CTs, i.e. lesion proximity. To ask if particular chromosome neighbourhoods could be identified we analysed all radiation-induced pair-wise exchanges using SCHIP (statistics for chromosome interphase positioning) and found that exchanges between chromosomes (1;13), (9;17), (9;18), (12;18) and (16;21) all occurred more often than expected assuming randomness. All of these pairs were also found to be either sharing similar preferred positions in interphase and/or sharing neighbouring territory boundaries. We also analysed a human small cell lung cancer cell line, DMS53, by M-FISH observing the genome to be highly rearranged, yet possessing rearrangements also involving chromosomes (1;13) and (9;17). Our findings show evidence for the occurrence of non-random exchanges that may reflect the territorial organisation of chromosomes in interphase at time of damage and highlight the importance of cellular geometry for the induction of aberrations of varying complexity after exposure to both low and high-LET radiation.Department of Healt

Tribimaximal Neutrino Mixing from A_4 Replication

Motivated by dimensional deconstruction, we propose a model of tribimaximal neutrino mixing based on A_4 x A_4 symmetry. In this model, the two triplet symmetry-breaking fields of conventional A_4 models are taken to transform under different A_4 group factors, but are not distinguished by any other quantum numbers. An additional bi-triplet flavon field breaks A_4 x A_4 to its diagonal subgroup. If the bi-triplet transforms under an additional Z_3 symmetry, we show that one can construct a general, renormalizable superpotential that yields the desired pattern of symmetry breaking. We identify the features that this model has in common with a deconstructed 5D theory in which A_4 is a subgroup of a continuous gauged flavor symmetry in the bulk.Comment: 13 pages LaTeX (v2: discussion added

The Significant Digit Law in Statistical Physics

The occurrence of the nonzero leftmost digit, i.e., 1, 2, ..., 9, of numbers from many real world sources is not uniformly distributed as one might naively expect, but instead, the nature favors smaller ones according to a logarithmic distribution, named Benford's law. We investigate three kinds of widely used physical statistics, i.e., the Boltzmann-Gibbs (BG) distribution, the Fermi-Dirac (FD) distribution, and the Bose-Einstein (BE) distribution, and find that the BG and FD distributions both fluctuate slightly in a periodic manner around the Benford distribution with respect to the temperature of the system, while the BE distribution conforms to it exactly whatever the temperature is. Thus the Benford's law seems to present a general pattern for physical statistics and might be even more fundamental and profound in nature. Furthermore, various elegant properties of Benford's law, especially the mantissa distribution of data sets, are discussed.Comment: 21 latex pages, 5 figures, final version in journal publicatio