Calcium signalling links MYC to NUAK1

NUAK1 is a member of the AMPK-related family of kinases. Recent evidence suggests that NUAK1 is an important regulator of cell adhesion and migration, cellular and organismal metabolism, and regulation of TAU stability. As such, NUAK1 may play key roles in multiple diseases ranging from neurodegeneration to diabetes and metastatic cancer. Previous work revealed a crucial role for NUAK1 in supporting viability of tumour cells specifically when MYC is overexpressed. This role is surprising, given that NUAK1 is activated by the tumour suppressor LKB1. Here we show that, in tumour cells lacking LKB1, NUAK1 activity is maintained by an alternative pathway involving calcium-dependent activation of PKCα. Calcium/PKCα-dependent activation of NUAK1 supports engagement of the AMPK-TORC1 metabolic checkpoint, thereby protecting tumour cells from MYC-driven cell death, and indeed, MYC selects for this pathway in part via transcriptional regulation of PKCα and ITPR. Our data point to a novel role for calcium in supporting tumour cell viability and clarify the synthetic lethal interaction between NUAK1 and MYC

Retrospective evaluation of foot-and-mouth disease vaccineeffectiveness in Turkey

AbstractFoot-and-mouth disease (FMD) is present in much of Turkey and its control is largely based on vaccination. The arrival of the FMD Asia-1 serotype in Turkey in 2011 caused particular concern, spreading rapidly westwards across the country towards the FMD free European Union. With no prior natural immunity, control of spread would rely heavily on vaccination.Unlike human vaccines, field protection is rarely evaluated directly for FMD vaccines. Between September 2011 and July 2012 we performed four retrospective outbreak investigations to assess the vaccine effectiveness (VE) of FMD Asia-1 vaccines in Turkey. Vaccine effectiveness is defined as the reduction in risk in vaccinated compared to unvaccinated individuals with similar virus exposure in the field.The four investigations included 12 villages and 1230 cattle >4 months of age. One investigation assessed the FMD Asia-1 Shamir vaccine, the other three evaluated the recently introduced FMD Asia-1 TUR 11 vaccine made using a field isolate of the FMD Asia-1 Sindh-08 lineage that had recently entered Turkey.After adjustment for confounding, the TUR 11 vaccine provided moderate protection against both clinical disease VE=69% [95% CI: 50%–81%] and infection VE=63% [95% CI: 29%–81%]. However, protection was variable with some herds with high vaccine coverage still experiencing high disease incidence. Some of this variability will be the result of the variation in virus challenge and immunity that occurs under field conditions.In the outbreak investigated there was no evidence that the Asia-1 Shamir vaccine provided adequate protection against clinical FMD with an incidence of 89% in single vaccinated cattle and 69% in those vaccinated two to five times.Based on these effectiveness estimates, vaccination alone is unlikely to produce the high levels of herd immunity needed to control FMD without additional control measures

Stability of Monomer-Dimer Piles

We measure how strong, localized contact adhesion between grains affects the maximum static critical angle, theta_c, of a dry sand pile. By mixing dimer grains, each consisting of two spheres that have been rigidly bonded together, with simple spherical monomer grains, we create sandpiles that contain strong localized adhesion between a given particle and at most one of its neighbors. We find that tan(theta_c) increases from 0.45 to 1.1 and the grain packing fraction, Phi, decreases from 0.58 to 0.52 as we increase the relative number fraction of dimer particles in the pile, nu_d, from 0 to 1. We attribute the increase in tan(theta_c(nu_d)) to the enhanced stability of dimers on the surface, which reduces the density of monomers that need to be accomodated in the most stable surface traps. A full characterization and geometrical stability analysis of surface traps provides a good quantitative agreement between experiment and theory over a wide range of nu_d, without any fitting parameters.Comment: 11 pages, 12 figures consisting of 21 eps files, submitted to PR

Prestressed fibre reinforced polymer (FRP) laminates for the strengthening of reinforced concrete structures

Recent development in the field of strengthening has seen the application of prestressing of FRP laminate prior to bonding in order to exploit its high tensile strength. The method of prestressing the laminate induces an initial tensile strain in the concrete beams upmost fibre, thus reducing the deflection of the beam throughout the design loads. This alteration of the beams structural characteristics provides advantages in beam serviceability requirements. Structurally the beam can withstand greater ultimate loads, while yielding of internal reinforcement and cracking moments are delayed substantially, compared to unlaminated beams. Extensive experimental investigations have been undertaken by many researchers with variables ranging from anchorage type, number of laminates applied to beam, tensile reinforcement ratio and the initial prestress level of laminates before bonding. Despite the large amount of experimental data in the field, current analytical models generally employ elementary procedures in predicting beam behaviour and as a result the analytical results exhibit poor correlation with the experimental results. This implies the necessity for the development of a generic model that can accurately predict beam behaviour that will be the basis of the present study. The focus of this paper is the development of a new analytical model that can accurately predict the behaviour of an RC beam strengthened with an externally bonded (EB) prestressed fibre reinforced polymer (FRP) laminate. The model will be critically compared to an experimental database for calibration purposes then applied in a parametric study

Optimal Sizes of Dielectric Microspheres for Cavity QED with Strong Coupling

The whispering gallery modes (WGMs) of quartz microspheres are investigated for the purpose of strong coupling between single photons and atoms in cavity quantum electrodynamics (cavity QED). Within our current understanding of the loss mechanisms of the WGMs, the saturation photon number, n, and critical atom number, N, cannot be minimized simultaneously, so that an "optimal" sphere size is taken to be the radius for which the geometric mean, (n x N)^(1/2), is minimized. While a general treatment is given for the dimensionless parameters used to characterize the atom-cavity system, detailed consideration is given to the D2 transition in atomic Cesium (852nm) using fused-silica microspheres, for which the maximum coupling coefficient g/(2*pi)=750MHz occurs for a sphere radius a=3.63microns corresponding to the minimum for n=6.06x10^(-6). By contrast, the minimum for N=9.00x10^(-6) occurs for a sphere radius of a=8.12microns, while the optimal sphere size for which (n x N)^(1/2) is minimized occurs at a=7.83microns. On an experimental front, we have fabricated fused-silica microspheres with radii a=10microns and consistently observed quality factors Q=0.8x10^(7). These results for the WGMs are compared with corresponding parameters achieved in Fabry-Perot cavities to demonstrate the significant potential of microspheres as a tool for cavity QED with strong coupling.Comment: 12 pages, 14 figure

Tracing PAH size in prominent nearby mid-infrared environments

Interstellar matter and star formatio

Surface Instability of Icicles

Quantitatively-unexplained stationary waves or ridges often encircle icicles. Such waves form when roughly 0.1 mm-thick layers of water flow down the icicle. These waves typically have a wavelength of 1cm approximately independent of external temperature, icicle thickness, and the volumetric rate of water flow. In this paper we show that these waves can not be obtained by naive Mullins-Sekerka instability, but are caused by a quite new surface instability related to the thermal diffusion and hydrodynamic effect of thin water flow.Comment: 11 pages, 5 figures, Late

The Mystery of Two Straight Lines in Bacterial Genome Statistics. Release 2007

In special coordinates (codon position--specific nucleotide frequencies) bacterial genomes form two straight lines in 9-dimensional space: one line for eubacterial genomes, another for archaeal genomes. All the 348 distinct bacterial genomes available in Genbank in April 2007, belong to these lines with high accuracy. The main challenge now is to explain the observed high accuracy. The new phenomenon of complementary symmetry for codon position--specific nucleotide frequencies is observed. The results of analysis of several codon usage models are presented. We demonstrate that the mean--field approximation, which is also known as context--free, or complete independence model, or Segre variety, can serve as a reasonable approximation to the real codon usage. The first two principal components of codon usage correlate strongly with genomic G+C content and the optimal growth temperature respectively. The variation of codon usage along the third component is related to the curvature of the mean-field approximation. First three eigenvalues in codon usage PCA explain 59.1%, 7.8% and 4.7% of variation. The eubacterial and archaeal genomes codon usage is clearly distributed along two third order curves with genomic G+C content as a parameter.Comment: Significantly extended version with new data for all the 348 distinct bacterial genomes available in Genbank in April 200

Rebirth of X-ray Emission from the Born-Again Planetary Nebula A 30

The planetary nebula (PN) A30 is believed to have undergone a very late thermal pulse resulting in the ejection of knots of hydrogen-poor material. Using HST images we have detected the angular expansion of these knots and derived an age of 850+280-150 yr. To investigate the spectral and spatial properties of the soft X-ray emission detected by ROSAT, we have obtained Chandra and XMM-Newton observations of A30. The X-ray emission from A30 can be separated into two components: a point-source at the central star and diffuse emission associated with the hydrogen-poor knots and the cloverleaf structure inside the nebular shell. To help us assess the role of the current stellar wind in powering this X-ray emission, we have determined the stellar parameters of the central star of A 30 using a non-LTE model fit to its optical and UV spectrum. The spatial distribution and spectral properties of the diffuse X-ray emission is suggestive that it is generated by the post-born-again and present fast stellar winds interacting with the hydrogen-poor ejecta of the born-again event. This emission can be attributed to shock-heated plasma, as the hydrogen-poor knots are ablated by the stellar winds, under which circumstances the efficient mass-loading of the present fast stellar wind raises its density and damps its velocity to produce the observed diffuse soft X-rays. Charge transfer reactions between the ions of the stellar winds and material of the born-again ejecta has also been considered as a possible mechanism for the production of diffuse X-ray emission, and upper limits on the expected X-ray production by this mechanism have been derived. The origin of the X-ray emission from the central star of A 30 is puzzling: shocks in the present fast stellar wind and photospheric emission can be ruled out, while the development of a new, compact hot bubble confining the fast stellar wind seems implausible.Comment: 29 pages, 11 figures, 4 tables; accepted for publication by Ap

The potential of small unmanned aircraft systems and structure-from-motion for topographic surveys: a test of emerging integrated approaches at Cwm Idwal, North Wales

This paper was accepted for publication in the journal Geomorphology and the definitive published version is available at http://dx.doi.org/10.1016/j.geomorph.2014.07.021Novel topographic survey methods that integrate both structure-from-motion (SfM) photogrammetry and small unmanned aircraft systems (sUAS) are a rapidly evolving investigative technique. Due to the diverse range of survey configurations available and the infancy of these new methods, further research is required. Here, the accuracy, precision and potential applications of this approach are investigated. A total of 543 images of the Cwm Idwal moraine–mound complex were captured from a light (b5 kg) semi-autonomous multi-rotor unmanned aircraft system using a consumer-grade 18 MP compact digital camera. The imageswere used to produce a DSM(digital surfacemodel) of themoraines. The DSMis in good agreement with 7761 total station survey points providing a total verticalRMSE value of 0.517mand verticalRMSE values as lowas 0.200mfor less densely vegetated areas of the DSM. High-precision topographic data can be acquired rapidly using this technique with the resulting DSMs and orthorectified aerial imagery at sub-decimetre resolutions. Positional errors on the total station dataset, vegetation and steep terrain are identified as the causes of vertical disagreement. Whilst this aerial survey approach is advocated for use in a range of geomorphological settings, care must be taken to ensure that adequate ground control is applied to give a high degree of accuracy