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)

Geometric construction of metaplectic covers of GLn in characteristic zero

This paper presents a new construction of the m-fold metaplectic cover of GLn over an algebraic number field k, where k contains a primitive m-th root of unity. A 2-cocycle on GLn(A) representing this extension is given and the splitting of the cocycle on GLn(k) is found explicitly. The cocycle is smooth at almost all places of k. As a consequence, a formula for the Kubota symbol on SLn is obtained. The construction of the paper requires neither class field theory nor algebraic K-theory, but relies instead on naive techniques from the geometry of numbers introduced by W. Habicht and T. Kubota. The power reciprocity law for a number field is obtained as a corollary

Modular forms on SU(2,1) with weight 1/3

In this note, we describe several new examples of holomorphic modular forms on the group SU(2,1). These forms are distinguished by having weight 13. We also describe a method for determining the levels at which one should expect to find such fractional weight forms

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

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

Non-residually Finite Extensions of Arithmetic Groups

The aim of the article is to show that there are many finite extensions of arithmetic groups which are not residually finite. Suppose G is a simple algebraic group over the rational numbers satisfying both strong approximation, and the congruence subgroup problem. We show that every arithmetic subgroup of G has finite extensions which are not residually finite. More precisely, we investigate the group H¯ 2 (Z/n) = lim → Γ H 2 (Γ ,Z/n), where Γ runs through the arithmetic subgroups of G. Elements of H¯ 2 (Z/n) correspond to (equivalence classes of) central extensions of arithmetic groups by Z/n; non-zero elements of H¯ 2 (Z/n) correspond to extensions which are not residually finite. We prove that H¯ 2 (Z/n) contains infinitely many elements of order n, some of which are invariant for the action of the arithmetic completion G[(Q) of G(Q). We also investigate which of these (equivalence classes of) extensions lift to characteristic zero, by determining the invariant elements in the group H¯ 2 (Zl) = lim ←t H¯ 2 (Z/l t ). We show that H¯ 2 (Zl) G[(Q) is isomorphic to Zl c for some positive integer c. When G(R) has no simple components of complex type, we prove that c = b+m, where b is the number of simple components of G(R) and m is the dimension of the centre of a maximal compact subgroup of G(R). In all other cases, we prove upper and lower bounds on c; our lower bound (which we believe is the correct number) is b+m

Prevalence of Obesity in Women of Accra, Ghana

The Women\'s Health Study of Accra, Ghana measured the burden of obesity and obesitylinked illnesses in urban women. This is a Cross-sectional community based study. 1328 adult women, age 18 years and older, were selected as a representative sampling of the women of Accra. A comprehensive medical history, physical examination and laboratory tests were performed. Overweight and obesity status was determined by calculating the body mass index (BMI) (kg/m2). BMI measurements are available for 1237 non-pregnant women. A total of 430 women (34.8%) were obese; 340 (27.4%) were overweight; 369 (29.8%) were normal weight; and 98 (8.0%) were underweight. Risk factors for obesity include age 50 to 70 years, OR 2.12 [1.72 -2.62], p 5 (p 34 years (

Barriers to innovation and sustainability at universities around the world

This paper explores the link between innovation and sustainability in the context of higher education, with the purpose of investigating the fundamental barriers for innovation and sustainable development in universities around the world. The method used involves both a quantitative and a qualitative approach, gathering the views of 301 experts from 172 universities across all continents. The results show that there are similar barriers across different geographical regions that require greater support from university administrations and management. In particular, the willingness of leaders, policy makers and decision-makers to envisage a sustainable future inside universities is often missing. Yet, without the support of senior management within a university, bottom-up sustainable initiatives seem destined to fail in the longer term due to a lack of investment and administrative support. This study also identifies that in order to yield the anticipated benefits, barriers need to be tackled in an integrated way, and that closer cooperation between sustainability researchers, university administrations and students is needed

Modelling-based evaluation of the costs, benefits and cost-effectiveness of multipathogen point-of-care tests for sexually transmitted infections in symptomatic genitourinary medicine clinic attendees

Objectives To quantify the costs, benefits and cost-effectiveness of three multipathogen point-of-care (POC) testing strategies for detecting common sexually transmitted infections (STIs) compared with standard laboratory testing. Design Modelling study. Setting Genitourinary medicine (GUM) services in England. Population A hypothetical cohort of 965 988 people, representing the annual number attending GUM services symptomatic of lower genitourinary tract infection. Interventions The decision tree model considered costs and reimbursement to GUM services associated with diagnosing and managing STIs. Three strategies using hypothetical point-of-care tests (POCTs) were compared with standard care (SC) using laboratory-based testing. The strategies were: A) dual POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); B) triplex POCT for CT-NG and Mycoplasma genitalium (MG); C) quadruplex POCT for CT-NG-MG and Trichomonas vaginalis (TV). Data came from published literature and unpublished estimates. Primary and secondary outcome measures Primary outcomes were total costs and benefits (quality-adjusted life years (QALYs)) for each strategy (2016 GB, £) and associated incremental cost-effectiveness ratios (ICERs) between each of the POC strategies and SC. Secondary outcomes were inappropriate treatment of STIs, onward STI transmission, pelvic inflammatory disease in women, time to cure and total attendances. Results In the base-case analysis, POC strategy C, a quadruplex POCT, was the most cost-effective relative to the other strategies, with an ICER of £36 585 per QALY gained compared with SC when using microcosting, and cost-savings of £26 451 382 when using tariff costing. POC strategy C also generated the most benefits, with 240 467 fewer clinic attendances, 808 fewer onward STI transmissions and 235 135 averted inappropriate treatments compared with SC. Conclusions Many benefits can be achieved by using multipathogen POCTs to improve STI diagnosis and management. Further evidence is needed on the underlying prevalence of STIs and SC delivery in the UK to reduce uncertainty in economic analyses