Galaxy destruction and diffuse light in clusters

Deep images of the Centaurus and Coma clusters reveal two spectacular arcs of diffuse light that stretch for over 100 kpc, yet are just a few kpc wide. At a surface brightness of m_b \sim 27-28th arcsec^-2, the Centaurus arc is the most striking example known of structure in the diffuse light component of a rich galaxy cluster. We use numerical simulations to show that the Centaurus feature can be reproduced by the tidal debris of a spiral galaxy that has been tidally disrupted by the gravitational potential of NGC 4709. The surface brightness and narrow dimensions of the diffuse light suggest that the disk was co-rotating with its orbital path past pericentre. Features this prominent in clusters will be relatively rare, although at fainter surface brightness levels the diffuse light will reveal a wealth of structure. Deeper imaging surveys may be able to trace this feature for several times its presently observed extent and somewhere along the tidal debris, a fraction of the original stellar component of the disk will remain bound, but transformed into a faint spheroidal galaxy. It should be possible to confirm the galactic origin of the Centaurus arc by observing planetary nebulae along its length with redshifts close to that of NGC 4709.Comment: Replaced with version accepted by MNRAS (Dec. 1999): Added missing reference (to pg. 4 & reference list). Section 3 shortened; removed three figures. Now 8 pages long, with 8 figures. Low resolution images included, high resolution version available at http://star-www.dur.ac.uk:80/~calcaneo/cenarc.htm

Nonlinear wakefields and electron injection in cluster plasma

Laser and beam driven wakefields promise orders of magnitude increases in electric field gradients for particle accelerators for future applications. Key areas to explore include the emittance properties of the generated beams and overcoming the dephasing limit in the plasma. In this paper, the first in-depth study of the self-injection mechanism into wakefield structures from non-homogeneous cluster plasmas is provided using high-resolution two dimensional particle-in-cell simulations. The clusters which are typical structures caused by ejection of gases from a high-pressure gas jet have a diameter much smaller than the laser wavelength. Conclusive evidence is provided for the underlying mechanism that leads to particle trapping, comparing uniform and cluster plasma cases. The accelerated electron beam properties are found to be tunable by changing the cluster parameters. The mechanism explains enhanced beam charge paired with large transverse momentum and energy which has implications for the betatron x-ray flux. Finally, the impact of clusters on the high-power laser propagation behavior is discussed

Sperm DNA methylation epimutation biomarker for paternal offspring autism susceptibility

Background: Autism spectrum disorder (ASD) has increased over tenfold over the past several decades and appears predominantly associated with paternal transmission. Although genetics is anticipated to be a component of ASD etiology, environmental epigenetics is now also thought to be an important factor. Epigenetic alterations, such as DNA methylation, have been correlated with ASD. The current study was designed to identify a DNA methylation signature in sperm as a potential biomarker to identify paternal offspring autism susceptibility.Methods and results: Sperm samples were obtained from fathers that have children with or without autism, and the sperm then assessed for alterations in DNA methylation. A genome-wide analysis (> 90%) for differential DNA methylation regions (DMRs) was used to identify DMRs in the sperm of fathers (n = 13) with autistic children in comparison with those (n = 13) without ASD children. The 805 DMR genomic features such as chromosomal location, CpG density and length of the DMRs were characterized. Genes associated with the DMRs were identified and found to be linked to previously known ASD genes, as well as other neurobiology-related genes. The potential sperm DMR biomarkers/diagnostic was validated with blinded test sets (n = 8-10) of individuals with an approximately 90% accuracy.Conclusions: Observations demonstrate a highly significant set of 805 DMRs in sperm that can potentially act as a biomarker for paternal offspring autism susceptibility. Ancestral or early-life paternal exposures that alter germline epigenetics are anticipated to be a molecular component of ASD etiology

Cost-effectiveness of screening for ovarian cancer amongst postmenopausal women: a model-based economic evaluation

Background The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was the biggest ovarian cancer screening trial to date. A non-significant effect of screening on ovarian cancer was reported, but the authors noted a potential delayed effect of screening, and suggested the need for four years further follow-up. There are no UK-based cost-effectiveness analyses of ovarian cancer screening. Hence we assessed the lifetime outcomes associated with, and the cost-effectiveness of, screening for ovarian cancer in the UK, along with the value of further research. Methods We performed a model-based economic evaluation. Effectiveness data were taken from UKCTOCS, which considered strategies of multimodal screening (MMS), ultrasound screening (USS) and no screening. We conducted systematic reviews to identify the remaining model inputs, and performed a rigorous and transparent prospective evaluation of different methods for extrapolating the effect of screening on ovarian cancer mortality. We considered costs to the UK healthcare system and measured effectiveness using quality-adjusted life years (QALYs). We used value of information methods to estimate the value of further research. Results Over a lifetime, MMS and USS were estimated to be both more expensive and more effective than no screening. USS was dominated by MMS, being both more expensive and less effective. Compared with no screening, MMS cost on average £419 more (95% confidence interval £255 to £578), and generated 0.047 more QALYs (0.002 to 0.088). The incremental cost-effectiveness ratio (ICER) comparing MMS with no screening was £8864 per QALY (£2600 to £51,576). Alternative extrapolation methods increased the ICER, with the highest value being £36,769 (£13,888 to dominated by no screening). Using the UKCTOCS trial horizon, both MMS and USS were dominated by no screening, as they produced fewer QALYs at a greater cost. The value of research into eliminating all uncertainty in long-term effectiveness was estimated to be worth up to £20 million, or approximately £5 million for four years follow-up. Conclusions Screening for ovarian cancer with MMS is both more effective and more expensive than not screening. Compared to national willingness to pay thresholds, lifetime cost-effectiveness is promising, but there remains considerable uncertainty regarding extrapolated long-term effectiveness

Using affective judgement to increase physical activity in British adults.

Mobile phone apps have been shown to increase physical activity (PA), but existing apps fail to target the emotional aspects of PA, which influence whether individuals are active. We developed an app that encourages individuals to focus on the emotional aspects of PA. We aimed to assess the acceptability of this app, and conduct a preliminary evaluation of efficacy. The app was developed in collaboration with users through focus groups. Seven users tested the app over 4 months and provided feedback on acceptability, aesthetics and functionality in a follow-up focus group. Results were summarized descriptively. Before testing the app, participants completed a questionnaire assessing their current PA and psychological antecedents of PA. A second questionnaire was completed at the follow-up focus group. Change scores are reported for each participant and overall. The social and reminder aspects facilitated motivation to be active and many found it easy to integrate into their lives. Most suggested modifications. Small improvements in number of minutes spent walking per week were observed (overall mean change +25 min) and some psychological antecedents of PA (overall mean change for social support for PA +0.14, self-efficacy for PA +0.17, outcome expectations about PA +0.20; all five-point scales), but reductions were seen in other domains. The app was acceptable to users, although developments are required. Testing with a small number of individuals, offering preliminary evidence of efficacy of this app, provides justification for further evaluation on a larger scale

Many Ribosomal Protein Genes Are Cancer Genes in Zebrafish

We have generated several hundred lines of zebrafish (Danio rerio), each heterozygous for a recessive embryonic lethal mutation. Since many tumor suppressor genes are recessive lethals, we screened our colony for lines that display early mortality and/or gross evidence of tumors. We identified 12 lines with elevated cancer incidence. Fish from these lines develop malignant peripheral nerve sheath tumors, and in some cases also other tumor types, with moderate to very high frequencies. Surprisingly, 11 of the 12 lines were each heterozygous for a mutation in a different ribosomal protein (RP) gene, while one line was heterozygous for a mutation in a zebrafish paralog of the human and mouse tumor suppressor gene, neurofibromatosis type 2. Our findings suggest that many RP genes may act as haploinsufficient tumor suppressors in fish. Many RP genes might also be cancer genes in humans, where their role in tumorigenesis could easily have escaped detection up to now

Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease

Expression of enzymatically inactive caspase-8, or deletion of caspase-8 from basal epidermal keratinocytes, triggers chronic skin inflammation in mice. Unlike similar inflammation resulting from arrest of nuclear factor κB activation in the epidermal cells, the effect induced by caspase-8 deficiency did not depend on TNF, IL-1, dermal macrophage function, or expression of the toll-like receptor adapter proteins MyD88 or TRIF. Both interferon regulatory factor (IRF) 3 and TANK-binding kinase were constitutively phosphorylated in the caspase-8–deficient epidermis, and knockdown of IRF3 in the epidermis-derived cells from these mice abolished the expression of up-regulated genes. Temporal and spatial analyses of the alterations in gene expression that result from caspase-8 deficiency reveal that the changes are initiated before birth, around the time that cornification develops, and occur mainly in the suprabasal layer. Finally, we found that caspase-8–deficient keratinocytes display an enhanced response to gene activation by transfected DNA. Our findings suggest that an enhanced response to endogenous activators of IRF3 in the epidermis, presumably generated in association with keratinocyte differentiation, contributes to the skin inflammatory process triggered by caspase-8 deficiency