An assessment of long duration geodynamo simulations using new paleomagnetic modeling criteria (Q PM)

Long-term temporal variations of the magnetic field (timescales >10 Myr), characterized from paleomagnetic data, have been hypothesized to reflect the evolution of Earth's deep interior and couplings between the core and mantle. By tying observed changes in the paleomagnetic record to mechanisms predicted from numerical geodynamo simulations, we have a unique tool for assessing changes in the deep interior back in time. However, numerical simulations are not run in an Earth-like parameter regime and assessing how well they reproduce the geomagnetic field is difficult. Criteria have been proposed to determine the level of spatial and temporal agreement between simulations and observations spanning historical and Holocene timescales, but no such criteria exist for longer timescales. Here we present a new set of five criteria (Quality of Paleomagnetic Modeling criteria, QPM) that assess the degree of semblance between a simulated dynamo and the temporal and spatial variations of the long-term (∼10 Myr) paleomagnetic field. These criteria measure inclination anomaly, virtual geomagnetic pole dispersion at the equator, latitudinal variation in virtual geomagnetic pole dispersion, normalized width of virtual dipole moment distribution, and dipole field reversals. We have assessed 46 geodynamo simulations using the QPM criteria. The simulations have each been run for the equivalent of at least ∼300 kyr, span reversing and non-reversing regimes, and include either homogeneous or heterogeneous heat flux boundary conditions. We find that none of our simulations reproduce all salient aspects of the long-term paleomagnetic field behavior for the past 10 Myr. Nevertheless, our simulations bracket Earth values, suggesting that an Earth-like simulation is feasible within the available computationally accessible parameter space. This new set of criteria can inform future simulations that aim to reproduce all aspects of Earth's long-term magnetic field behavior

Dynamo constraints on the long-term evolution of Earth's magnetic field strength

Elucidating the processes in the liquid core that have produced observed palaeointensity changes over the last 3.5 Gyr is crucial for understanding the dynamics and long-term evolution of Earth’s deep interior. We combine numerical geodynamo simulations with theoretical scaling laws to investigate the variation of Earth’s magnetic field strength over geological time. Our approach follows the study of Aubert et al., adapted to include recent advances in numerical simulations, mineral physics and palaeomagnetism. We first compare the field strength within the dynamo region and on the core–mantle boundary (CMB) between a suite of 314 dynamo simulations and two power-based theoretical scaling laws. The scaling laws are both based on a Quasi-Geostropic (QG) force balance at leading order and a Magnetic, Archimedian, and Coriolis (MAC) balance at first order and differ in treating the characteristic length scale of the convection as fixed (QG-MAC-fixed) or determined as part of the solution (QG-MAC-free). When the data set is filtered to retain only simulations with magnetic to kinetic energy ratios greater than at least two we find that the internal field together with the root-mean-square and dipole CMB fields exhibit power-law behaviour that is compatible with both scalings within uncertainties arising from different heating modes and boundary conditions. However, while the extrapolated intensity based on the QG-MAC-free scaling matches Earth’s modern CMB field, the QG-MAC-fixed prediction shoots too high and also significantly overestimates palaeointensities over the last 3.5 Gyr. We combine the QG-MAC-free scaling with outputs from 275 realizations of core–mantle thermal evolution to construct synthetic true dipole moment (TDM) curves spanning the last 3.5 Gyr. Best-fitting TDMs reproduce binned PINT data during the Bruhnes and before inner core nucleation (ICN) within observational uncertainties, but PINT does not contain the predicted strong increase and subsequent high TDMs during the early stages of inner core growth. The best-fitting models are obtained for a present-day CMB heat flow of 11–16 TW, increasing to 17–22 TW at 4 Ga, and predict a minimum TDM at ICN

Interaction Between Convection and Pulsation

This article reviews our current understanding of modelling convection dynamics in stars. Several semi-analytical time-dependent convection models have been proposed for pulsating one-dimensional stellar structures with different formulations for how the convective turbulent velocity field couples with the global stellar oscillations. In this review we put emphasis on two, widely used, time-dependent convection formulations for estimating pulsation properties in one-dimensional stellar models. Applications to pulsating stars are presented with results for oscillation properties, such as the effects of convection dynamics on the oscillation frequencies, or the stability of pulsation modes, in classical pulsators and in stars supporting solar-type oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages, 14 figure

Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer

A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5′-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5′-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer

A creative industries perspective on creativity and culture

The chapter considers changing definitions of creativity in relation to UK cultural policy and practice in the creative industries. Three perspectives are introduced, beginning with the notion of creativity as a product of individual creativity and talent, popularised by the UK government’s 1998 Creative Industries Mapping Document. This perspective is contrasted with an older model of creativity as a collective expression of shared values, as emphasised in earlier cultural industries policies of the 1970s and 1980s. Finally, the chapter considers contemporary views of creativity in the creative industries as participatory, user-generated, remixed and ‘democratized’. The chapter concludes that there is value in all three perspectives—the challenge for policy makers, managers and practitioners in the creative industries is connecting together individual self-expression with collective cultural values

Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer

BACKGROUND: The discovery of ERG/ETV1 gene rearrangements and PTEN gene loss warrants investigation in a mechanism-based prognostic classification of prostate cancer (PCa). The study objective was to evaluate the potential clinical significance and natural history of different disease categories by combining ERG/ETV1 gene rearrangements and PTEN gene loss status. METHODS: We utilised fluorescence in situ hybridisation (FISH) assays to detect PTEN gene loss and ERG/ETV1 gene rearrangements in 308 conservatively managed PCa patients with survival outcome data. RESULTS: ERG/ETV1 gene rearrangements alone and PTEN gene loss alone both failed to show a link to survival in multivariate analyses. However, there was a strong interaction between ERG/ETV1 gene rearrangements and PTEN gene loss (P<0.001). The largest subgroup of patients (54%), lacking both PTEN gene loss and ERG/ETV1 gene rearrangements comprised a 'good prognosis' population exhibiting favourable cancer-specific survival (85.5% alive at 11 years). The presence of PTEN gene loss in the absence of ERG/ETV1 gene rearrangements identified a patient population (6%) with poorer cancer-specific survival that was highly significant (HR=4.87, P<0.001 in multivariate analysis, 13.7% survival at 11 years) when compared with the 'good prognosis' group. ERG/ETV1 gene rearrangements and PTEN gene loss status should now prospectively be incorporated into a predictive model to establish whether predictive performance is improved. CONCLUSIONS: Our data suggest that FISH studies of PTEN gene loss and ERG/ETV1 gene rearrangements could be pursued for patient stratification, selection and hypothesis-generating subgroup analyses in future PCa clinical trials and potentially in patient management

Brokering Trust to Enhance Leadership: A Self-Monitoring Approach to Leadership Emergence

What kind of person is likely to emerge as an informal leader in the workplace? Experimental research shows that high self-monitors—who tend to adjust their attitudes and behaviors to the demands of different situations—emerge as informal leaders in temporary groups. By contrast, low self-monitors—who tend to be true to themselves in terms of consistency in attitudes and behaviors across different situations—are less likely to emerge as leaders. But this prior research does not address the criticism that the emergence of high self-monitors as leaders represents ephemeral impression management in the context of laboratory experiments. To address this issue, we collected and analyzed data from a 116-member high-technology firm. Our results show that self-monitoring is related not only to leadership emergence, but also to the provision of advice to co-workers. Further, people who occupied brokerage positions (being trusted by those who did not trust each other) tended to be seen as leaders if they were high rather than low self-monitors. From these results, we build a picture of the high self-monitoring emergent leader as someone who notices problems and ameliorates them through the provision of advice and the brokerage of relationships across social divides. The occupation of a structurally advantageous position may well be more advantageous for some (i.e., high self-monitors) relative to others (i.e., low self-monitors)

Gender-Associated Genes in Filarial Nematodes Are Important for Reproduction and Potential Intervention Targets

Lymphatic filariasis is a neglected tropical disease that is caused by thread-like parasitic worms that live and reproduce in lymphatic vessels of the human host. There are no vaccines to prevent filariasis, and available drugs are not effective against all stages of the parasite. In addition, recent reports suggest that the filarial nematodes may be developing resistance to key medications. Therefore, there is an urgent need to identify new drug targets in filarial worms. The purpose of this study was to perform a genome-wide analysis of gender-associated gene transcription to improve understanding of key reproductive processes in filarial nematodes. Our results indicate that thousands of genes are differentially expressed in male and female adult worms. Many of those genes are involved in specific reproductive processes such as embryogenesis and spermatogenesis. In addition, expression of some of those genes is suppressed by tetracycline, a drug that leads to sterilization of adult female worms in many filarial species. Thus, gender-associated genes represent priority targets for design of vaccines and drugs that interfere with reproduction of filarial nematodes. Additional work with this type of integrated systems biology approach should lead to important new tools for controlling filarial diseases

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively