DNMTs are required for delayed genome instability caused by radiation

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited - Copyright @ 2012 Landes Bioscience.The ability of ionizing radiation to initiate genomic instability has been harnessed in the clinic where the localized delivery of controlled doses of radiation is used to induce cell death in tumor cells. Though very effective as a therapy, tumor relapse can occur in vivo and its appearance has been attributed to the radio-resistance of cells with stem cell-like features. The molecular mechanisms underlying these phenomena are unclear but there is evidence suggesting an inverse correlation between radiation-induced genomic instability and global hypomethylation. To further investigate the relationship between DNA hypomethylation, radiosensitivity and genomic stability in stem-like cells we have studied mouse embryonic stem cells containing differing levels of DNA methylation due to the presence or absence of DNA methyltransferases. Unexpectedly, we found that global levels of methylation do not determine radiosensitivity. In particular, radiation-induced delayed genomic instability was observed at the Hprt gene locus only in wild-type cells. Furthermore, absence of Dnmt1 resulted in a 10-fold increase in de novo Hprt mutation rate, which was unaltered by radiation. Our data indicate that functional DNMTs are required for radiation-induced genomic instability, and that individual DNMTs play distinct roles in genome stability. We propose that DNMTS may contribute to the acquirement of radio-resistance in stem-like cells.This study is funded by NOTE, BBSRC and the Royal Society Dorothy Hodgkin Research Fellowship

A piloted simulator study on augmentation systems to improve helicopter flying qualities in terrain flight

Four basic single-rotor helicopters, one teetering, on articulated, and two hingeless, which were found to have a variety of major deficiencies in a previous fixed-based simulator study, were selected as baseline configurations. The stability and control augmentation systems (SCAS) include simple control augmentation systems to decouple pitch and yaw responses due to collective input and to quicken the pitch and roll control responses; SCAS of rate-command type designed to optimize the sensitivity and damping and to decouple the pitch-roll due to aircraft angular tate; and attitude-command type SCAS. Pilot ratings and commentary are presented as well as performance data related to the task. SCAS control usages and their gain levels associated with specific rotor types are also discussed

Learning organisations: A literature review and critique

Approved for Public Release - UnclassifiedA literature review on the Learning Organisation field was conducted, examining the dominant assumptions and creating a solid foundation for the practical application of the learning organisation concept to the Australian Army. In order to examine the literature's dominant assumptions, we asked the following questions: (i) What are the various meanings attributed to learning organisations?; (ii) What sorts of learnings are privileged within the literature?; (iii) What are the key characteristics or "building blocks" that make up a learning organisation? We discovered that the learning organisation construct represents an evolution from bureaucratic and performance-based organisational form to innovative and flexible organisations. In surveying the literature, other factors found to impact on learning organisations included cognitive, social, cultural, technological and structural elements. For example, learning organisations apply increasingly sophisticated understanding of knowledge and personnel management to best exploit their social, intellectual and knowledge capital. In contrast, some factors are not adequately explored in the literature; for example, the significance of power relations, hierarchy and authority on learning within and by organisations has not been fully elucidated. There is an increasing number of studies investigating the direct impact of developing a learner-centric approach on organisational outcomes; the number of studies linking learning to improved organisational performance is growing. There are real, significant and measureable benefits of developing the learning capabilities of an organisation.Steven Talbot, Christina Stothard, Maya Drobnjak and Denise McDowal

Laminin and fibronectin in rectal adenocarcinoma: relationship to tumour grade, stage and metastasis.

Using an immunoperoxidase procedure, we have examined the distribution of laminin and fibronectin in normal human large intestinal mucosa and in 50 cases of rectal adenocarcinoma for which extensive clinical follow up was available. In normal tissue, laminin staining was largely restricted to basement membranes, including that underlying the epithelial cells, whereas fibronectin was found in both basement membranes and surrounding connective tissue. In rectal carcinomas, basement membrane-like staining for laminin associated with tumour cells was found in only 27 out of the 50 cases studied. Statistical analysis showed that the presence of laminin-containing basement membranes was correlated with low histological grade (well-differentiated tumours), but not with stage (progression through the bowel wall and the development of lymph node metastases) and, in a highly significant way, with a reduced incidence of distant metastases and increased patient survival. Although fibronectin was found in tumour cell basement membranes where these were present, it was also found in the stroma of all 50 tumours. There was no apparent correlation between the presence of stromal fibronectin and grade, stage or development of metastases. Finally, attention is drawn to some of the technical difficulties in detecting basement membrane antigens in formalin-fixed tissue, the material most frequently available for retrospective study

Characterization of aerosol associated with enhanced small particle number concentrations in a suburban forested environment

Two elevated particle number/mass growth events associated with Aitken‐mode particles were observed during a sampling campaign (13–29 September 2004) at the Duke University Free‐Air CO2 Enrichment facility, a forested field site located in suburban central North Carolina. Aerosol growth rates between 1.2 and 4.9 nm hr−1 were observed, resulting in net increases in geometric mean diameter of 21 and 37 nm during events. Growth was dominated by addition of oxidized organic compounds. Campaign‐average aerosol mass concentrations measured by an Aerodyne quadrupole aerosol mass spectrometer (Q‐AMS) were 1.9 ± 1.6 (σ), 1.6 ± 1.9, 0.1 ± 0.1, and 0.4 ± 0.4 μg m−3 for organic mass (OM), sulfate, nitrate, and ammonium, respectively. These values represent 47%, 40%, 3%, and 10%, respectively, of the measured submicron aerosol mass. Based on Q‐AMS spectra, OM was apportioned to hydrocarbon‐like organic aerosol (HOA, likely representing primary organic aerosol) and two types of oxidized organic aerosol (OOA‐1 and OOA‐2), which constituted on average 6%, 58%, and 36%, respectively, of the apportioned OM. OOA‐1 probably represents aged, regional secondary organic aerosol (SOA), while OOA‐2 likely reflects less aged SOA. Organic aerosol characteristics associated with the events are compared to the campaign averages. Particularly in one event, the contribution of OOA‐2 to overall OM levels was enhanced, indicating the likelihood of less aged SOA formation. Statistical analyses investigate the relationships between HOA, OOA‐1, OOA‐2, other aerosol components, gas‐phase species, and meteorological data during the campaign and individual events. No single variable clearly controls the occurrence of a particle growth event

An electron Talbot interferometer

The Talbot effect, in which a wave imprinted with transverse periodicity reconstructs itself at regular intervals, is a diffraction phenomenon that occurs in many physical systems. Here we present the first observation of the Talbot effect for electron de Broglie waves behind a nanofabricated transmission grating. This was thought to be difficult because of Coulomb interactions between electrons and nanostructure gratings, yet we were able to map out the entire near-field interference pattern, the "Talbot carpet", behind a grating. We did this using a Talbot interferometer, in which Talbot interference fringes from one grating are moire'-filtered by a 2nd grating. This arrangement has served for optical, X-ray, and atom interferometry, but never before for electrons. Talbot interferometers are particularly sensitive to distortions of the incident wavefronts, and to illustrate this we used our Talbot interferometer to measure the wavefront curvature of a weakly focused electron beam. Here we report how this wavefront curvature demagnified the Talbot revivals, and we discuss applications for electron Talbot interferometers.Comment: 5 pages, 5 figures, updated version with abstrac