DNA double-strand break distributions in X-ray and alpha-particle irradiated V79 cells: Evidence for non-random breakage

Many studies have shown that with increasing LET of ionizing radiation the RBE (relative biological effectiveness) for dsb (double strand breaks) induction remains around 1.0 despite the increase in the RBE for cell killing. This has been attributed to an increase in the complexity of lesions, classified as dsb with current techniques, at multiply damaged sites. This study determines the molecular weight distributions of DNA from Chinese hamster V79 cells irradiated with X-rays or 110 keV/mu m alpha-particles. Two running conditions for pulsed-field gel-electrophoresis were chosen to give optimal separation of fragments either in the 225 kbp-5.7 Mbp range or the 0.3 kbp to 225 kbp range. Taking the total fraction of DNA migrating into the gel as a measure of fragmentation, the RBE for dsb induction was less than 1.0 for both molecular weight regions studied. The total yields of dsb were 8.2 x 10(-9) dsb/Gy/bp for X-rays and 7.8 x 10(-9) dsb/Gy/bp for a-particles, measured using a random breakage model. Analysis of the RBE of alpha-particles versus molecular weight gave a different response. In the 0.4 Mbp-57 Mbp region the RBE was less than 1.0; however, below 0.4 Mbp the RBE increased above 1.0. The frequency distributions of fragment sizes were found to differ from those predicted by a model assuming random breakage along the length of the DNA and the differences were greater for alpha-particles than for X-rays. An excess of fragments induced by a single-hit mechanism was found in the 8-300 kbp region and for X-rays and alpha-particles these corresponded to an extra 0.8 x 10(-9) and 3.4 x 10(-9) dsb/bp/Gy, respectively. Thus for every alpha-particle track that induces a dsb there is a 44% probability of inducing a second break within 300 kbp and for electron tracks the probability is 10%. This study shows that the distribution of damage from a high LET alpha-particle track is significantly different from that observed with low LET X-rays. In particular, it suggests that the fragmentation patterns of irradiated DNA may be related to the higher-order chromatin repealing structures found in intact cells.

We Never Give Up II

Ten years after the production of the initial 'We Never Give Up' film, this documentary filmis a follow-up film about the experiences of ten survivors of South Africa apartheid and their struggle for reparations. Produced by the Human Rights Media Centre, Cape Town, the film was directed and filmed by Cahal McLaughlin in a collaborative relationship with Khulumani Support Group Western Cape.

Further Information:

This documentary film, produced with the Human Rights Media Centre, Cape Town, and in collaboration with Khulumani Support Group Western Cape, is the ten-year follow up to We Never Give Up (2002), which addressed the issues of reparations as dealt with by the South African government and the Truth and Reconciliation Commission. We Never Give Up II (2012) returns to these themes and to the same participants, asking how life has changed in the interim. The process of collaborative practices acknowledges the importance of sharing ownership/authorship in the storytelling processes as well as in validating traumatic experiences by those who survived major and sustained political violence. Made over a two-year period, involving close consultation with participants, the film offers insights, by those most directly affected, to what might constitute legal, financial, social and psychological reparations. The film has been screened in Cape Town, Bloemfontain, Zanzibar Film Festival, Belfast (Belfast Film Festival), Brighton, Guildford, Galway and London, always accompanied by discussion of the issues raised in Q&As. To emphasise the importance of the film for debates on policy around reparations, a 25 minute edited version was selected to be screened on SABC on ‘Special Assignment’ by SABC on April 29th, 2013 (South Africa’s ‘Freedom Day’), followed by a debate with Department of Justice spokesperson, Dr Khotso De Wee. The chapter 'Maureen Never Gave Up' in Daniels, McLaughlin and Pearce (eds.) 'Truth, Dare or Promise' (2013) Cambridge Scholars Press (ISBN: 1-4438-4959-6, ISBN 13: 978-1-4438-4959-3, Release Date: 2013-09-01), which analyses the production of this film, is offered as part of the portfolio.

Testing the Prebish-Singer hypothesis using second-generation panel data stationarity tests with a break

In this paper, we test the Prebish-Singer (PS) hypothesis, which states that real commodity prices decline in the long run, using two recent powerful panel data stationarity tests accounting for cross-sectional dependence and a structural break. We find that the hypothesis cannot be rejected for most commodities other than oil.

Numbered-up gas-liquid micro/milli channels reactor with modular flow distributor

Gas-liquid processing in microreactors remains mostly restricted to the laboratory scale due to the complexity and expenditure needed for an adequate numbering-up with a uniform flow distribution. Here, the numbering-up is presented for multi-phase (gas-liquid) flow in microreactor suitable for a production capacity of kg/h. Based on the barrier channels concept, the barrier-based micro/milli reactor (BMMR) is designed and fabricated to deliver flow non-uniformity of less than 10%. The BMMR consists of eight parallel channels all operated in the Taylor flow regime and with a liquid flow rate up to 150. mL/min. The quality of the flow distribution is reported by studying two aspects. The first aspect is the influence of different viscosities, surface tensions and flow rates. The second aspect is the influence of modularity by testing three different reaction channels type: (1) square channels fabricated in a stainless steel plate, (2) square channels fabricated in a glass plate, and (3) circular channels (capillaries) made of stainless steel. Additionally, the BMMR is compared to that of a single channel regard the slug and bubble lengths and bubble generation frequency. The results pave the ground for bringing multi-phase flow in microreactor one step closer for large scale production via numbering-up. © 2012 Elsevier B.V.

Moving to evidence-based practice in long-term care:the role of a Best Practise Resource Centre in two long-term care settings.

In this article, the authors provide an overview on the development of a Long-Term Care Best Practise Resource Centre. The results of both a feasibility study and the outcomes of a 1-year demonstration project are presented. The demonstration project involved a hospital as the information service provider and two demonstration sites, a home care service agency and a nursing home that used the services of the Centre. The goals of the Centre were threefold: provide access to literature for staff in long-term care (LTC) settings; improve the information management skills of health care providers; and support research and the integration of best practices in LTC organizations. The results of the pilot study contributed to the development of a collaborative information access system for LTC clinicians and managers that provides timely, up-to-date information contributing to improving the quality of care for adults receiving LTC. Based on this demonstration project, strategies for successful innovation in LTC are identified.

A long-term follow-up of cognitive, emotional, and behavioural sequelae to Reye syndrome

Eighteen adolescents who had survived Reye syndrome (RS) in early childhood were assessed on cognitive, emotional, and behavioural variables in a second follow-up study tracking this group. Siblings were used as controls. The entire group with RS had survived with no obvious neurological damage at the first follow-up study. Indeed, current findings suggested that long-term cognitive, emotional, and behavioural functioning was comparable to siblings in approximately half of the group with RS. However, two factors were associated with a less favourable outcome. Cognitive, emotional, and behavioural functioning were significantly poorer in the subgroup of survivors whose illness had occurred in the first year of life. In addition, loss of consciousness, although the association with poor outcome was not as noticeable, was also associated with relative deficits on some scales of cognitive ability. Many of these deficits had not been obvious at the first follow-up and the importance of neurodevelopmental factors are considered. Finally, the implications of these findings for research and interventions in RS and other such encephalopathies are discussed.

Cooperative Learning in Science: Follow-up from primary to high school

This paper reports a two-year longitudinal study of the effects of cooperative learning on science attainment, attitudes towards science, and social connectedness during transition from primary to high school. A previous project on cooperative learning in primary schools observed gains in science understanding and in social aspects of school life. This project followed 204 children involved in the previous project and 440 comparison children who were not as they undertook transition from 24 primary schools to 16 high schools. Cognitive, affective, and social gains observed in the original project survived transition. The implications improving the effectiveness of school transition by using cooperative learning initiatives are explored. Possibilities for future research and the implications for practice and policy are discussed.

DNA double strand break repair: a radiation perspective

SIGNIFICANCE:
Ionizing radiation (IR) can induce a wide range of unique deoxyribonucleic acid (DNA) lesions due to the spatiotemporal correlation of the ionization produced. Of these, DNA double strand breaks (DSBs) play a key role. Complex mechanisms and sophisticated pathways are available within cells to restore the integrity and sequence of the damaged DNA molecules.
RECENT ADVANCES:
Here we review the main aspects of the DNA DSB repair mechanisms with emphasis on the molecular pathways, radiation-induced lesions, and their significance for cellular processes.
CRITICAL ISSUES:
Although the main characteristics and proteins involved in the two DNA DSB repair processes present in eukaryotic cells (homologous recombination and nonhomologous end-joining) are reasonably well established, there are still uncertainties regarding the primary sensing event and their dependency on the complexity, location, and time of the damage. Interactions and overlaps between the different pathways play a critical role in defining the repair efficiency and determining the cellular functional behavior due to unrepaired/miss-repaired DNA lesions. The repair pathways involved in repairing lesions induced by soluble factors released from directly irradiated cells may also differ from the established response mechanisms.
FUTURE DIRECTIONS:
An improved understanding of the molecular pathways involved in sensing and repairing damaged DNA molecules and the role of DSBs is crucial for the development of novel classes of drugs to treat human diseases and to exploit characteristics of IR and alterations in tumor cells for successful radiotherapy applications.

Impact of a play-based curriculum in the first two years of primary school: literacy and numeracy outcomes over seven years

In 2000–2002 an innovative early years curriculum, the Enriched Curriculum (EC), was introduced
into 120 volunteer schools across Northern Ireland, replacing a traditional curriculum similar to
others across the UK at that time. It was intended by the designers to be developmentally appropriate
and play-based with the primary goal of preventing the experience of persistent early failure in
children. The EC was not intended to be a literacy and numeracy intervention, yet it did considerably
alter pedagogy in these domains, particularly the age at which formal reading and mathematics
instruction began. As part of a multi-method evaluation running from 2000–2008, the research
team followed the primary school careers of the first two successive cohorts of EC children, comparing
them with year-ahead controls attending the same 24 schools. Compared to the year-ahead control
group, the findings show that the EC children’s reading and mathematics scores fell behind in
the first two years but the majority of EC children caught up by the end of their fourth year. Thereafter,
the performance of the first EC cohort fell away slightly, while that of the second continued to
match that of controls. Overall, the play-based curriculum had no statistically significant positive
effects on reading and mathematics in the medium term. At best, the EC children’s scores matched
those of controls.

Genome-wide scans of three independent sets of 90 Irish multiplex schizophrenia families and follow-up of selected regions in all families provides evidence for multiple susceptibility genes

From our linkage study of Irish families with a high density of schizophrenia, we have previously reported evidence for susceptibility genes in regions 5q21-31, 6p24-21, 8p22-21, and 10p15-p11. In this report, we describe the cumulative results from independent genome scans of three a priori random subsets of 90 families each, and from multipoint analysis of all 270 families in ten regions. Of these ten regions, three (13q32, 18p11-q11, and 18q22-23) did not generate scores above the empirical baseline pairwise scan results, and one (6q13-26) generated a weak signal. Six other regions produced more positive pairwise and multipoint results. They showed the following maximum multipoint H-LOD (heterogeneity LOD) and NPL scores: 2p14-13: 0.89 (P = 0.06) and 2.08 (P = 0.02), 4q24-32: 1.84 (P = 0.007) and 1.67 (P = 0.03), 5q21-31: 2.88 (P= 0.0007), and 2.65 (P = 0.002), 6p25-24: 2.13 (P = 0.005) and 3.59 (P = 0.0005), 6p23: 2.42 (P = 0.001) and 3.07 (P = 0.001), 8p22-21: 1.57 (P = 0.01) and 2.56 (P = 0.005), 10p15-11: 2.04 (P = 0.005) and 1.78 (P = 0.03). The degree of 'internal replication' across subsets differed, with 5q, 6p, and 8p being most consistent and 2p and 10p being least consistent. On 6p, the data suggested the presence of two susceptibility genes, in 6p25-24 and 6p23-22. Very few families were positive on more than one region, and little correlation between regions was evident, suggesting substantial locus heterogeneity. The levels of statistical significance were modest, as expected from loci contributing to complex traits. However, our internal replications, when considered along with the positive results obtained in multiple other samples, suggests that most of these six regions are likely to contain genes that influence liability to schizophrenia.

Fluid Shear Induces Conformation Change in Human Blood Protein von Willebrand Factor in Solution

Many of the physiological functions of von Willebrand Factor (VWF), including its binding interaction with blood platelets, are regulated by the magnitude of applied fluid/hydrodynamic stress. We applied two complementary strategies to study the effect of fluid forces on the solution structure of VWF. First, small-angle neutron scattering was used to measure protein conformation changes in response to laminar shear rates (G) up to 3000/s. Here, purified VWF was sheared in a quartz Couette cell and protein conformation was measured in real time over length scales from 2-140 nm. Second, changes in VWF structure up to 9600/s were quantified by measuring the binding of a fluorescent probe 1,1'-bis(anilino)-4-,4'-bis(naphtalene)-8,8'-disulfonate (bis-ANS) to hydrophobic pockets exposed in the sheared protein. Small angle neutron scattering studies, coupled with quantitative modeling, showed that VWF undergoes structural changes at G < 3000/s. These changes were most prominent at length scales <10 nm (scattering vector (q) range >0.6/nm). A mathematical model attributes these changes to the rearrangement of domain level features within the globular section of the protein. Studies with bis-ANS demonstrated marked increase in bis-ANS binding at G > 2300/s. Together, the data suggest that local rearrangements at the domain level may precede changes at larger-length scales that accompany exposure of protein hydrophobic pockets. Changes in VWF conformation reported here likely regulate protein function in response to fluid shear.

The internal structure of asteroid (25143) Itokawa as revealed by detection of YORP spin-up *’**

Context. Near-Earth asteroid (25143) Itokawa was visited by the Hayabusa spacecraft in 2005, resulting in a highly detailed shape and surface topography model. This model has led to several predictions for the expected radiative torques on this asteroid, suggesting that its spin rate should be decelerating. Aims. To detect changes in rotation rate that may be due to YORP-induced radiative torques, which in turn may be used to investigate the interior structure of the asteroid. Methods. Through an observational survey spanning 2001 to 2013 we obtained rotational lightcurve data at various times over the last five close Earth-approaches of the asteroid. We applied a polyhedron-shape-modelling technique to assess the spin-state of the asteroid and its long term evolution. We also applied a detailed thermophysical analysis to the shape model determined from the Hayabusa spacecraft. Results. We have successfully measured an acceleration in Itokawa's spin rate of dω/dt = (3.54 ± 0.38) × 10 rad day, equivalent to a decrease of its rotation period of ~45 ms year. From the thermophysical analysis we find that the centre-of-mass for Itokawa must be shifted by ~21 m along the long-axis of the asteroid to reconcile the observed YORP strength with theory. Conclusions. This can be explained if Itokawa is composed of two separate bodies with very different bulk densities of 1750 ± 110 kg m and 2850 ± 500 kg m, and was formed from the merger of two separate bodies, either in the aftermath of a catastrophic disruption of a larger differentiated body, or from the collapse of a binary system. We therefore demonstrate that an observational measurement of radiative torques, when combined with a detailed shape model, can provide insight into the interior structure of an asteroid. Futhermore, this is the first measurement of density inhomogeneity within an asteroidal body, that reveals significant internal structure variation. A specialised spacecraft is normally required for this.

Adolescent ecstasy use and depression: cause and effect, or two outcomes of home environment?

Background: This study assessed the association between adolescent ecstasy use and depressive symptoms in adolescence. Methods: The Belfast Youth Development Study surveyed a cohort annually from age 11 to 16 years. Gender, Strengths and Difficulties Questionnaire emotional subscale, living arrangements, parental affluence, parent and peer attachment, tobacco, alcohol, cannabis and ecstasy use were investigated as predictors of Short Mood and Feelings Questionnaire (SMFQ) outcome. Results: Of 5371 respondents, 301 (5.6%) had an SMFQ > 15, and 1620 (30.2) had missing data for SMFQ. Around 8% of the cohort had used ecstasy by the end of follow-up. Of the non-drug users, ∼2% showed symptoms of depression, compared with 6% of those who had used alcohol, 6% of cannabis users, 6% of ecstasy users and 7% of frequent ecstasy users. Without adjustment, ecstasy users showed around a 4-fold increased odds of depressive symptoms compared with non-drug users [odds ratio (OR) = 0.26; 95% confidence interval (CI) = 0.10, 0.68]. Further adjustment for living arrangements, peer and parental attachment attenuated the association to under a 3-fold increase (OR = 0.37; 95% CI = 0.15, 0.94). There were no differences by frequency of use. Conclusions: Ecstasy use during adolescence may be associated with poorer mental health; however, this association can be explained by the confounding social influence of family dynamics. These findings could be used to aid effective evidence-based drug policies, which concentrate criminal justice and public health resources on reducing harm.

Direct Detection of YORP Spin-up on Asteroid (25143) Itokawa and Implications for its Internal Structure

Near-Earth asteroid (25143) Itokawa was visited by the Hayabusa spacecraft in 2005, resulting in a highly detailed surface shape and topography model. This model has led to several predictions for the expected radiative torques on this asteroid, suggesting that its spin rate should be decelerating. Through an observational survey spanning 2001 to 2013 we have successfully measured an acceleration in its spin rate of dω/dt = 3.54 (± 0.38) × 10^(-8) rad day^(-2), equivalent to a decrease of its rotation period of ~ 45 ms year^(-1). Using the shape model determined from the Hayabusa spacecraft, we applied a detailed thermophysical analysis, to reconcile the predicted YORP strength with that observed. We find that the center-of-mass for Itokawa must be shifted by ~20 m along the long-axis of the asteroid to reconcile observations with theory. This can be explained if Itokawa is composed of two separate bodies with very different bulk densities of 1740 ± 110 kg m^(-3) and 2730 ± 440 kg m^(-3), and was formed from the merger of two separate bodies, consistent with the collapse of a binary system or the re-accumulation of material from a catastrophic collisional disruption. We demonstrate that an observational measurement of radiative torques, when combined with a detailed shape model, can provide insight into the interior structure of an asteroid.

Toward Unconstrained Ear Recognition From Two-Dimensional Images

Ear recognition, as a biometric, has several advantages. In particular, ears can be measured remotely and are also relatively static in size and structure for each individual. Unfortunately, at present, good recognition rates require controlled conditions. For commercial use, these systems need to be much more robust. In particular, ears have to be recognized from different angles ( poses), under different lighting conditions, and with different cameras. It must also be possible to distinguish ears from background clutter and identify them when partly occluded by hair, hats, or other objects. The purpose of this paper is to suggest how progress toward such robustness might be achieved through a technique that improves ear registration. The approach focuses on 2-D images, treating the ear as a planar surface that is registered to a gallery using a homography transform calculated from scale-invariant feature-transform feature matches. The feature matches reduce the gallery size and enable a precise ranking using a simple 2-D distance algorithm. Analysis on a range of data sets demonstrates the technique to be robust to background clutter, viewing angles up to +/- 13 degrees, and up to 18% occlusion. In addition, recognition remains accurate with masked ear images as small as 20 x 35 pixels.