Time-distance analysis of the emerging active region NOAA 10790

We investigate the emergence of Active Region NOAA 10790 by means of time – distance helioseismology. Shallow regions of increased sound speed at the location of increased magnetic activity are observed, with regions becoming deeper at the locations of sunspot pores. We also see a long-lasting region of decreased sound speed located underneath the region of the flux emergence, possibly relating to a temperature perturbation due to magnetic quenching of eddy diffusivity, or to a dense flux tube. We detect and track an object in the subsurface layers of the Sun characterised by increased sound speed which could be related to emerging magnetic-flux and thus obtain a provisional estimate of the speed of emergence of around 1 km s−1

Development and validation of a NanoString BASE47 bladder cancer gene classifier

Background Recent molecular characterization of urothelial cancer (UC) has suggested potential pathways in which to direct treatment, leading to a host of targeted therapies in development for UC. In parallel, gene expression profiling has demonstrated that high-grade UC is a heterogeneous disease. Prognostic basal-like and luminal-like subtypes have been identified and an accurate transcriptome BASE47 classifier has been developed. However, these phenotypes cannot be broadly investigated due to the lack of a clinically viable diagnostic assay. We sought to develop and evaluate a diagnostic classifier of UC subtype with the goal of accurate classification from clinically available specimens. Methods Tumor samples from 52 patients with high-grade UC were profiled for BASE47 genes concurrently by RNAseq as well as NanoString. After design and technical validation of a BASE47 NanoString probeset, results from the RNAseq and NanoString were used to translate diagnostic criteria to the Nanostring platform. Evaluation of repeatability and accuracy was performed to derive a final Nanostring based classifier. Diagnostic classification resulting from the NanoString BASE47 classifier was validated on an independent dataset (n = 30). The training and validation datasets accurately classified 87% and 93% of samples, respectively. Results Here we have derived a NanoString-platform BASE47 classifier that accurately predicts basal-like and luminal-like subtypes in high grade urothelial cancer. We have further validated our new NanoString BASE47 classifier on an independent dataset and confirmed high accuracy when compared with our original Transcriptome BASE47 classifier. Conclusions The NanoString BASE47 classifier provides a faster turnaround time, a lower cost per sample to process, and maintains the accuracy of the original subtype classifier for better clinical implementation

Solar Polar Fields During Cycles 21 --- 23: Correlation with Meridional Flows

We have examined polar magnetic fields for the last three solar cycles, {$\it{viz.}$}, cycles 21, 22 and 23 using NSO Kitt Peak synoptic magnetograms. In addition, we have used SoHO/MDI magnetograms to derive the polar fields during cycle 23. Both Kitt Peak and MDI data at high latitudes (78${^{\circ}}$--90${^{\circ}}$) in both solar hemispheres show a significant drop in the absolute value of polar fields from the late declining phase of the solar cycle 22 to the maximum of the solar cycle 23. We find that long term changes in the absolute value of the polar field, in cycle 23, is well correlated with changes in meridional flow speeds that have been reported recently. We discuss the implication of this in influencing the extremely prolonged minimum experienced at the start of the current cycle 24 and in forecasting the behaviour of future solar cycles.Comment: 4 Figures 11 pages; Revised version under review in Solar Physic

Helioseismology of Sunspots: A Case Study of NOAA Region 9787

Various methods of helioseismology are used to study the subsurface properties of the sunspot in NOAA Active Region 9787. This sunspot was chosen because it is axisymmetric, shows little evolution during 20-28 January 2002, and was observed continuously by the MDI/SOHO instrument. (...) Wave travel times and mode frequencies are affected by the sunspot. In most cases, wave packets that propagate through the sunspot have reduced travel times. At short travel distances, however, the sign of the travel-time shifts appears to depend sensitively on how the data are processed and, in particular, on filtering in frequency-wavenumber space. We carry out two linear inversions for wave speed: one using travel-times and phase-speed filters and the other one using mode frequencies from ring analysis. These two inversions give subsurface wave-speed profiles with opposite signs and different amplitudes. (...) From this study of AR9787, we conclude that we are currently unable to provide a unified description of the subsurface structure and dynamics of the sunspot.Comment: 28 pages, 18 figure

Meridional Circulation and Global Solar Oscillations

We investigate the influence of large-scale meridional circulation on solar p-modes by quasi-degenerate perturbation theory, as proposed by \cite{lavely92}. As an input flow we use various models of stationary meridional circulation obeying the continuity equation. This flow perturbs the eigenmodes of an equilibrium model of the Sun. We derive the signatures of the meridional circulation in the frequency multiplets of solar p-modes. In most cases the meridional circulation leads to negative average frequency shifts of the multiplets. Further possible observable effects are briefly discussed.Comment: 14 pages, 5 figures, submittted to Solar Physics Topical Issue "HELAS

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

EPO does not promote interaction between the erythropoietin and beta-common receptors

A direct interaction between the erythropoietin (EPOR) and the beta-common (βc) receptors to form an Innate Repair Receptor (IRR) is controversial. On one hand, studies have shown a functional link between EPOR and βc receptor in tissue protection while others have shown no involvement of the βc receptor in tissue repair. To date there is no biophysical evidence to confirm a direct association of the two receptors either in vitro or in vivo. We investigated the existence of an interaction between the extracellular regions of EPOR and the βc receptor in silico and in vitro (either in the presence or absence of EPO or EPO-derived peptide ARA290). Although a possible interaction between EPOR and βc was suggested by our computational and genomic studies, our in vitro biophysical analysis demonstrates that the extracellular regions of the two receptors do not specifically associate. We also explored the involvement of the βc receptor gene (Csf2rb) under anaemic stress conditions and found no requirement for the βc receptor in mice. In light of these studies, we conclude that the extracellular regions of the EPOR and the βc receptor do not directly interact and that the IRR is not involved in anaemic stress.Karen S. Cheung Tung Shing, Sophie E. Broughton, Tracy L. Nero, Kevin Gillinder, Melissa D. Ilsley, Hayley Ramshaw, Angel F. Lopez, Michael D. W. Griffin, Michael W. Parker, Andrew C. Perkins, Urmi Dhaga

Advances in Global and Local Helioseismology: an Introductory Review

Helioseismology studies the structure and dynamics of the Sun's interior by observing oscillations on the surface. These studies provide information about the physical processes that control the evolution and magnetic activity of the Sun. In recent years, helioseismology has made substantial progress towards the understanding of the physics of solar oscillations and the physical processes inside the Sun, thanks to observational, theoretical and modeling efforts. In addition to the global seismology of the Sun based on measurements of global oscillation modes, a new field of local helioseismology, which studies oscillation travel times and local frequency shifts, has been developed. It is capable of providing 3D images of the subsurface structures and flows. The basic principles, recent advances and perspectives of global and local helioseismology are reviewed in this article.Comment: 86 pages, 46 figures; "Pulsation of the Sun and Stars", Lecture Notes in Physics, Vol. 832, Rozelot, Jean-Pierre; Neiner, Coralie (Eds.), 201

Modeling the Subsurface Structure of Sunspots

While sunspots are easily observed at the solar surface, determining their subsurface structure is not trivial. There are two main hypotheses for the subsurface structure of sunspots: the monolithic model and the cluster model. Local helioseismology is the only means by which we can investigate subphotospheric structure. However, as current linear inversion techniques do not yet allow helioseismology to probe the internal structure with sufficient confidence to distinguish between the monolith and cluster models, the development of physically realistic sunspot models are a priority for helioseismologists. This is because they are not only important indicators of the variety of physical effects that may influence helioseismic inferences in active regions, but they also enable detailed assessments of the validity of helioseismic interpretations through numerical forward modeling. In this paper, we provide a critical review of the existing sunspot models and an overview of numerical methods employed to model wave propagation through model sunspots. We then carry out an helioseismic analysis of the sunspot in Active Region 9787 and address the serious inconsistencies uncovered by \citeauthor{gizonetal2009}~(\citeyear{gizonetal2009,gizonetal2009a}). We find that this sunspot is most probably associated with a shallow, positive wave-speed perturbation (unlike the traditional two-layer model) and that travel-time measurements are consistent with a horizontal outflow in the surrounding moat.Comment: 73 pages, 19 figures, accepted by Solar Physic