On the helicity characteristics and induced emf of magnetic-Coriolis wave packets

In a rapidly rotating Boussinesq fluid, buoyant anomalies radiate low-frequency inertial wave packets which disperse along the rotation axis. The wave packets lead to axially elongated vortices, which propagate negative (positive) kinetic helicity upwards (downwards) with respect to the rotation vector. The kinetic helicity carried by the inertial wave packets is near-maximal, relative to the velocity and vorticity fields. In classical mean-field theory, kinetic helicity is often associated with the α-effect, which is thought to be an important ingredient for planetary dynamos. The modification of inertial wave packets in the presence of a transverse uniform magnetic field is investigated here, motivated by small-scale dynamics in planetary cores, where a large-scale magnetic field affects fluid motions. We study numerically the dispersion of wave packets from an isolated buoyant source and from a random layer of buoyant anomalies, while varying the Lehnert number Le – the ratio of the frequencies of Alfvén and inertial waves. We find that for Le < 0.1, the vortices are columnar and continue to segregate kinetic helicity so that it is negative (positive) above (below) the buoyant source. Importantly, the wave packets induce an α-effect, which remains strong and coherent for Earth-like values of the Lehnert number (Le < 0.1). The interaction of wave packets emitted by multiple neighbouring buoyant sources results in an α-effect that is stronger than the α-effect induced by wave packets launched from an isolated buoyant source, and we provide an analytical explanation for this. The coherence of the α-effect induced by the wave packets, for Earth-like values of the Lehnert number, lends support to the α2 dynamo model driven by helical waves

A physical conjecture for the dipolar-multipolar dynamo transition

In numerical simulations of planetary dynamos there is an abrupt transition in the dynamics of both the velocity and magnetic fields at a ‘local’ Rossby number of 0.1. For smaller Rossby numbers there are helical columnar structures aligned with the rotation axis, which efficiently maintain a dipolar field. However, when the thermal forcing is increased, these columns break down and the field becomes multi-polar. Similarly, in rotating turbulence experiments and simulations there is a sharp transition at a Rossby number of ${\sim}0.4$. Again, helical axial columnar structures are found for lower Rossby numbers, and there is strong evidence that these columns are created by inertial waves, at least on short time scales. We perform direct numerical simulations of the flow induced by a layer of buoyant anomalies subject to strong rotation, inspired by the equatorially biased heat flux in convective planetary dynamos. We assess the role of inertial waves in generating columnar structures. At high rotation rates (or weak forcing) we find columnar flow structures that segregate helicity either side of the buoyant layer, whose axial length scale increases linearly, as predicted by the theory of low-frequency inertial waves. As the rotation rate is weakened and the magnitude of the buoyant perturbations is increased, we identify a portion of the flow which is more strongly three-dimensional. We show that the flow in this region is turbulent, and has a Rossby number above a critical value $Ro^{crit}\sim 0.4$, consistent with previous findings in rotating turbulence. We suggest that the discrepancy between the transition value found here (and in rotating turbulence experiments), and that seen in the numerical dynamos ($Ro^{crit}\sim 0.1$), is a result of a different choice of the length scale used to define the local $Ro$. We show that when a proxy for the flow length scale perpendicular to the rotation axis is used in this definition, the numerical dynamo transition lies at $Ro^{crit}\sim 0.5$. Based on this we hypothesise that inertial waves, continually launched by buoyant anomalies, sustain the columnar structures in dynamo simulations, and that the transition documented in these simulations is due to the inability of inertial waves to propagate for Ro>Ro^{crit}.The Leverhulme Trust U

Exploration of the Mid-Cayman Rise

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TRAP1 chaperone protein mutations and autoinflammation

We identified a consanguineous kindred, of three affected children with severe autoinflammation, resulting in the death of one sibling and allogeneic stem cell transplantation in the other two. All three were homozygous for MEFV p.S208C mutation; however, their phenotype was more severe than previously reported, prompting consideration of an oligogenic autoinflammation model. Further genetic studies revealed homozygous mutations in TRAP1, encoding the mitochondrial/ER resident chaperone protein tumour necrosis factor receptor associated protein 1 (TRAP1). Identification of a fourth, unrelated patient with autoinflammation and compound heterozygous mutation of TRAP1 alone facilitated further functional studies, confirming the importance of this protein as a chaperone of misfolded proteins with loss of function, which may contribute to autoinflammation. Impaired TRAP1 function leads to cellular stress and elevated levels of serum IL-18. This study emphasizes the importance of considering digenic or oligogenic models of disease in particularly severe phenotypes and suggests that autoinflammatory disease might be enhanced by bi-allelic mutations in TRAP1

Integrating complex genomic datasets and tumour cell sensitivity profiles to address a 'simple' question: which patients should get this drug?

It is becoming increasingly apparent that cancer drug therapies can only reach their full potential through appropriate patient selection. Matching drugs and cancer patients has proven to be a complex challenge, due in large part to the substantial molecular heterogeneity inherent to human cancers. This is not only a major hurdle to the improvement of the use of current treatments but also for the development of novel therapies and the ability to steer them to the relevant clinical indications. In this commentary we discuss recent studies from Kuo et al., published this month in BMC Medicine, in which they used a panel of cancer cell lines as a model for capturing patient heterogeneity at the genomic and proteomic level in order to identify potential biomarkers for predicting the clinical activity of a novel candidate chemotherapeutic across a patient population. The findings highlight the ability of a 'systems approach' to develop a better understanding of the properties of novel candidate therapeutics and to guide clinical testing and application

Identification and validation of oncologic miRNA biomarkers for Luminal A-like breast cancer

Introduction: Breast cancer is a common disease with distinct tumor subtypes phenotypically characterized by ER and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression, and altered miRNA expression has been demonstrated in a variety of cancer states presenting the potential for exploitation as cancer biomarkers. Blood provides an excellent medium for biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A-like (ER+PR+HER2/neu-) breast cancer and their effectiveness as oncologic biomarkers in the clinical setting. Methods: Blood samples were prospectively collected from patients with Luminal A-like breast cancer (n=54) and controls (n=56). RNA was extracted, reverse transcribed and subjected to microarray analysis (n=10 Luminal A-like; n=10 Control). Differentially expressed miRNAs were identified by artificial neural network (ANN) data-mining algorithms. Expression of specific miRNAs was validated by RQ-PCR (n=44 Luminal A; n=46 Control) and potential relationships between circulating miRNA levels and clinicopathological features of breast cancer were investigated. Results: Microarray analysis identified 76 differentially expressed miRNAs. ANN revealed 10 miRNAs for further analysis ( miR-19b, miR-29a, miR-93, miR-181a, miR-182, miR-223, miR-301a, miR-423-5p, miR-486-5 and miR-652 ). The biomarker potential of 4 miRNAs ( miR-29a, miR-181a , miR-223 and miR-652 ) was confirmed by RQ-PCR, with significantly reduced expression in blood of women with Luminal A-like breast tumors compared to healthy controls (p=0.001, 0.004, 0.009 and 0.004 respectively). Binary logistic regression confirmed that combination of 3 of these miRNAs ( miR-29a, miR-181a and miR-652 ) could reliably differentiate between cancers and controls with an AUC of 0.80. Conclusion: This study provides insight into the underlying molecular portrait of Luminal A-like breast cancer subtype. From an initial 76 miRNAs, 4 were validated with altered expression in the blood of women with Luminal A-like breast cancer. The expression profiles of these 3 miRNAs, in combination with mammography, has potential to facilitate accurate subtype- specific breast tumor detection

In search of innovative capabilities of communities of practice : a systematic review and typology for future research

The concept of communities of practice has generated considerable debate among scholars of management. Attention has shifted from a concern with the transmission and reproduction of knowledge towards their utility for enhancing innovative potential. Questions of governance, power, collaboration and control have all entered the debate with different theorizations emerging from a wide mix of empirical research. We appraise these key findings through a critical review of the literature. From a divergent range of findings, we identify four main ways in which communities of practice enable and constrain innovative capabilities as (a) enablers of learning for innovation, (b) situated platforms for professional occupations, (c) dispersed collaborative environments and (d) governance structures designed for purpose. Our conclusion signals the way forward for further research that could be used to improve our understanding of different contextual forms and how they may align with organizations in enabling rather than constraining innovative capabilities

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

The role of contracting strategies in social value implementation

There has been an increasing demand for social value (SV) implementation to assume a cardinal position in the infrastructure delivery efforts of infrastructure client organisations (ICOs). However, whereas successful implementation has been recorded in some projects, monumental failures have also been recorded in others. This variance in implementation performance is a cause for concern. The mode of governance applied in an infrastructure delivery endeavour has been identified as capable of influencing the implementation of SV. This observation makes imperative an investigation into the role of contracting strategies – an integral part of governance modes – adopted by ICOs on SV implementation performance. This is the aim of this study. Using a case study approach, three infrastructure projects which used different contracting strategies were selected from two different countries, the UK and Nigeria. Semistructured interviews were conducted with ICO representatives on these projects and subsequently analysed using qualitative content analysis. Findings confirmed that the kind of contract adopted by ICOs influenced their ability to drive the successful implementation of desirable SV objectives through their supply chain. It is therefore recommended that ICOs ensure that the selected contracting strategies are capable of ensuring successful implementation of the desired objectives

Fatal myocarditis in a child with systemic onset juvenile idiopathic arthritis during treatment with an interleukin 1 receptor antagonist

<p>Abstract</p> <p>Background</p> <p>The pathologic diagnosis of isolated myocarditis without pericardial involvement is uncommonly encountered in systemic onset Juvenile Idiopathic Arthritis (soJIA).</p> <p>Case</p> <p>An eleven year-old boy with soJIA died suddenly while being treated with the interleukin 1 (IL-1) receptor inhibitor, anakinra. His autopsy revealed an enlarged heart and microscopic findings were consistent with myocarditis, but not pericarditis. Viral PCR testing performed on his myocardial tissue was negative.</p> <p>Conclusion</p> <p>This case illustrates myocarditis as a fatal complication of soJIA, potentially enabled by anakinra.</p