In situ electron holography of the dynamic magnetic field emanating from a hard-disk drive writer

The proliferation of mobile devices in society accessing data via the ‘cloud’ is imposing a dramatic increase in the amount of information to be stored on hard disk drives (HDD) used in servers. Forecasts are that areal densities will need to increase by as much as 35% compound per annum and by 2020 cloud storage capacity will be around 7 zettabytes corresponding to areal densities of 2 Tb/in2. This requires increased performance from the magnetic pole of the electromagnetic writer in the read/write head in the HDD. Current state-of-art writing is undertaken by morphologically complex magnetic pole of sub 100 nm dimensions, in an environment of engineered magnetic shields and it needs to deliver strong directional magnetic field to areas on the recording media around 50 nm x 13 nm. This points to the need for a method to perform direct quantitative measurements of the magnetic field generated by the write pole at the nanometer scale. Here we report on the complete in situ quantitative mapping of the magnetic field generated by a functioning write pole in operation using electron holography. Opportunistically, it points the way towards a new nanoscale magnetic field source to further develop in situ Transmission Electron Microscopy.

A review of high magnetic moment thin films for microscale and nanotechnology applications

The creation of large magnetic fields is a necessary component in many technologies, ranging from magnetic resonance imaging, electric motors and generators, and magnetic hard disk drives in information storage. This is typically done by inserting a ferromagnetic pole piece with a large magnetisation density MS in a solenoid. In addition to large MS, it is usually required or desired that the ferromagnet is magnetically soft and has a Curie temperature well above the operating temperature of the device. A variety of ferromagnetic materials are currently in use, ranging from FeCo alloys in, for example, hard disk drives, to rare earth metals operating at cryogenic temperatures in superconducting solenoids. These latter can exceed the limit on MS for transition metal alloys given by the Slater-Pauling curve. This article reviews different materials and concepts in use or proposed for technological applications that require a large MS, with an emphasis on nanoscale material systems, such as thin and ultra-thin films. Attention is also paid to other requirements or properties, such as the Curie temperature and magnetic softness. In a final summary, we evaluate the actual applicability of the discussed materials for use as pole tips in electromagnets, in particular, in nanoscale magnetic hard disk drive read-write heads; the technological advancement of the latter has been a very strong driving force in the development of the field of nanomagnetism.

Chemical abundances in the inner 5 kpc of the Galactic disk

High-resolution, high signal-to-noise spectral data are presented for four young B-type stars lying towards the Galactic Centre. Determination of their atmospheric parameters from their absorption line profiles, and uvby photometric measurement of the continua indicate that they are massive objects lying slightly out of the plane, and were probably born in the disk between 2.5-5 kpc from the Centre. We have carried out a detailed absolute and differential line-by-line abundance analyses of the four stars compared to two stars with very similar atmospheric parameters in the solar neighbourhood. The stars appear to be rich in all the well sampled chemical elements (C, N, Si, Mg, S, Al), except for oxygen. Oxygen abundances derived in the atmospheres of these four stars are very similar to that in the solar neighbourhood. If the photospheric composition of these young stars is reflective of the gaseous ISM in the inner Galaxy, then the values derived for the enhanced metals are in excellent agreement with the extrapolation of the Galactic abundance gradients previously derived by Rolleston et al. (2000) and others. However, the data for oxygen suggests that the inner Galaxy may not be richer than normal in this element, and the physical reasons for such a scenario are unclear.

Size-selective fishing drives species composition in the Celtic Sea

Fishing alters community size structure by selectively removing larger individual fish and by changing the relative abundance of different-sized species. To assess the relative importance of individual-and species-level effects, two indices of fish community structure were compared, the relative abundance of large fish individuals (large fish indicator, LFI) and the relative abundance of large fish species (large species indicator, LSI). The two indices were strongly correlated for empirical data from the Celtic Sea and for data from simulated model communities, suggesting that much of the variability in the LFI is caused by shifts in the relative abundance of species (LSI). This correlation is explained by the observation that most of the biomass of a given species is spread over few length classes, a range spanning the factor 2 of individual length, such that most species contributed predominantly to either the small or the large component of the LFI. The results suggest that the effects of size-selective fishing in the Celtic Sea are mediated mainly through changes in community composition.

Reproducibility of optic disk topographic measurements with the Topcon ImageNet and the Heidelberg Retina Tomograph

Objective: To compare the reproducibility of optic disk measurements provided by an image analyzer and a scanning laser tomograph. Methods: Ten images of the same eye of 10 normal volunteers were taken with the Heidelberg Retina Tomograph and with the Topcon ImageNet. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) were used to evaluate the reproducibility of the measurements. Results: Eleven parameters were analyzed with the Topcon ImageNet. Six parameters (55%) had ICC greater than 90%. Four parameters (36%) had CV less than 10%. Twelve parameters were evaluated with the Heidelberg Retina Tomograph. Nine parameters (75%) had ICC over 90%. Nine parameters (75%) had CV less than 10%. Conclusion: Both systems provided reproducible data. The optic disk parameters provided by the Heidelberg Retina Tomograph had a better reproducibility than those obtained from the Topcon ImageNet.

Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal pigment epithelium suggests potential mechanism that drives the onset of choroidal angiogenesis in mice

Whilst data recognise both myeloid cell accumulation during choroidal neovascularisation (CNV) as well as complement activation, none of the data has presented a clear explanation for the angiogenic drive that promotes pathological angiogenesis. One possibility that is a pre-eminent drive is a specific and early conditioning and activation of the myeloid cell infiltrate. Using a laser-induced CNV murine model, we have identified that disruption of retinal pigment epithelium (RPE) and Bruch's membrane resulted in an early recruitment of macrophages derived from monocytes and microglia, prior to angiogenesis and contemporaneous with lesional complement activation. Early recruited CD11b(+) cells expressed a definitive gene signature of selective inflammatory mediators particularly a pronounced Arg-1 expression. Accumulating macrophages from retina and peripheral blood were activated at the site of injury, displaying enhanced VEGF expression, and notably prior to exaggerated VEGF expression from RPE, or earliest stages of angiogenesis. All of these initial events, including distinct VEGF (+) Arg-1(+) myeloid cells, subsided when CNV was established and at the time RPE-VEGF expression was maximal. Depletion of inflammatory CCR2-positive monocytes confirmed origin of infiltrating monocyte Arg-1 expression, as following depletion Arg-1 signal was lost and CNV suppressed. Furthermore, our in vitro data supported a myeloid cell uptake of damaged RPE or its derivatives as a mechanism generating VEGF (+) Arg-1(+) phenotype in vivo. Our results reveal a potential early driver initiating angiogenesis via myeloid-derived VEGF drive following uptake of damaged RPE and deliver an explanation of why CNV develops during any of the stages of macular degeneration and can be explored further for therapeutic gain.

In situ diagnostics and prognostics of solder fatigue in IGBT modules for electric vehicle drives

This paper proposes an in situ diagnostic and prognostic (D&P) technology to monitor the health condition of insulated gate bipolar transistors (IGBTs) used in EVs with a focus on the IGBTs' solder layer fatigue. IGBTs' thermal impedance and the junction temperature can be used as health indicators for through-life condition monitoring (CM) where the terminal characteristics are measured and the devices' internal temperature-sensitive parameters are employed as temperature sensors to estimate the junction temperature. An auxiliary power supply unit, which can be converted from the battery's 12-V dc supply, provides power to the in situ test circuits and CM data can be stored in the on-board data-logger for further offline analysis. The proposed method is experimentally validated on the developed test circuitry and also compared with finite-element thermoelectrical simulation. The test results from thermal cycling are also compared with acoustic microscope and thermal images. The developed circuitry is proved to be effective to detect solder fatigue while each IGBT in the converter can be examined sequentially during red-light stopping or services. The D&P circuitry can utilize existing on-board hardware and be embedded in the IGBT's gate drive unit.

p63 drives invasion in keratinocytes expressing HPV16 E6/E7 genes through regulation of Src-FAK signalling

Using microarray information from oro-pharyngeal data sets and results from primary human foreskin keratinocytes (HFK) expressing Human Papilloma Virus (HPV)-16 E6/E7 proteins, we show that p63 expression regulates signalling molecules which initiate cell migration such as Src and focal adhesion kinase (FAK) and induce invasion in 3D-organotypic rafts; a phenotype that can be reversed by depletion of p63. Knockdown of Src or FAK in the invasive cells restored focal adhesion protein paxillin at cell periphery and impaired the cell migration. In addition, specific inhibition of FAK (PF573228) or Src (dasatinib) activities mitigated invasion and attenuated the expression/activity of matrix metalloproteinase 14 (MMP14), a pivotal MMP in the MMP activation cascade. Expression of constitutively active Src in non-invasive HFK expressing E6/E7 proteins upregulated the activity of c-Jun and MMP14, and induced invasion in rafts. Depletion of Src, FAK or AKT in the invasive cells normalised the expression/activity of c-Jun and MMP14, thus implicating the Src-FAK/AKT/AP-1 signalling in MMP14-mediated extra-cellular matrix remodelling. Up-regulation of Src, AP-1, MMP14 and p63 expression was confirmed in oro-pharyngeal cancer. Since p63 transcriptionally regulated expression of many of the genes in this signalling pathway, it suggests that it has a central role in cancer progression.

Coastal upwelling drives intertidal assemblage structure and trophic ecology

ecosystems. Coastal oceanic upwelling, for example, has been associated with elevatedbiomass and abundance patterns of certain functional groups, e.g., corticated macroalgae.In the upwelling system of Northern Chile, we examined measures of intertidal macrobenthiccomposition, structure and trophic ecology across eighteen shores varying in theirproximity to two coastal upwelling centres, in a hierarchical sampling design (spatial scalesof >1 and >10 km). The influence of coastal upwelling on intertidal communities was confirmedby the stable isotope values (δ13C and δ15N) of consumers, including a dominantsuspension feeder, grazers, and their putative resources of POM, epilithic biofilm, andmacroalgae. We highlight the utility of muscle δ15N from the suspension feeding mussel,Perumytilus purpuratus, as a proxy for upwelling, supported by satellite data and previousstudies. Where possible, we used corrections for broader-scale trends, spatial autocorrelation,ontogenetic dietary shifts and spatial baseline isotopic variation prior to analysis. Ourresults showed macroalgal assemblage composition, and benthic consumer assemblagestructure, varied significantly with the intertidal influence of coastal upwelling, especiallycontrasting bays and coastal headlands. Coastal topography also separated differences inconsumer resource use. This suggested that coastal upwelling, itself driven by coastlinetopography, influences intertidal communities by advecting nearshore phytoplankton populationsoffshore and cooling coastal water temperatures. We recommend the isotopic valuesof benthic organisms, specifically long-lived suspension feeders, as in situ alternativesto offshore measurements of upwelling influence

A Lightweight Tool for Anomaly Detection in Cloud Data Centres

Cloud data centres are critical business infrastructures and the fastest growing service providers. Detecting anomalies in Cloud data centre operation is vital. Given the vast complexity of the data centre system software stack, applications and workloads, anomaly detection is a challenging endeavour. Current tools for detecting anomalies often use machine learning techniques, application instance behaviours or system metrics distribu- tion, which are complex to implement in Cloud computing environments as they require training, access to application-level data and complex processing. This paper presents LADT, a lightweight anomaly detection tool for Cloud data centres that uses rigorous correlation of system metrics, implemented by an efficient corre- lation algorithm without need for training or complex infrastructure set up. LADT is based on the hypothesis that, in an anomaly-free system, metrics from data centre host nodes and virtual machines (VMs) are strongly correlated. An anomaly is detected whenever correlation drops below a threshold value. We demonstrate and evaluate LADT using a Cloud environment, where it shows that the hosting node I/O operations per second (IOPS) are strongly correlated with the aggregated virtual machine IOPS, but this correlation vanishes when an application stresses the disk, indicating a node-level anomaly.

Mutant p53 expression in fallopian tube epithelium drives cell migration

Ovarian cancer is the fifth leading cause of cancer death among US women. Evidence supports the hypothesis that high-grade serous ovarian cancers (HGSC) may originate in the distal end of the fallopian tube. Although a heterogeneous disease, 96% of HGSC contain mutations in p53. In addition, the "p53 signature," or overexpression of p53 protein (usually associated with mutation), is a potential precursor lesion of fallopian tube derived HGSC suggesting an essential role for p53 mutation in early serous tumorigenesis. To further clarify p53-mutation dependent effects on cells, murine oviductal epithelial cells (MOE) were stably transfected with a construct encoding for the R273H DNA binding domain mutation in p53, the most common mutation in HGSC. Mutation in p53 was not sufficient to transform MOE cells but did significantly increase cell migration. A similar p53 mutation in murine ovarian surface epithelium (MOSE), another potential progenitor cell for serous cancer, was not sufficient to transform the cells nor change migration suggesting tissue specific effects of p53 mutation. Microarray data confirmed expression changes of pro-migratory genes in p53(R273H) MOE compared to parental cells, which could be reversed by suppressing Slug expression. Combining p53(R273H) with KRAS(G12V) activation caused transformation of MOE into high-grade sarcomatoid carcinoma when xenografted into nude mice. Elucidating the specific role of p53(R273H) in the fallopian tube will improve understanding of changes at the earliest stage of transformation. This information can help develop chemopreventative strategies to prevent the accumulation of additional mutations and reverse progression of the "p53 signature" thereby, improving survival rates.

Divergent androgen regulation of unfolded protein response pathways drives prostate cancer

The unfolded protein response (UPR) is a homeostatic mechanism to maintain endoplasmic reticulum (ER) function. The UPR is activated by various physiological conditions as well as in disease states, such as cancer. As androgens regulate secretion and development of the normal prostate and drive prostate cancer (PCa) growth, they may affect UPR pathways. Here, we show that the canonical UPR pathways are directly and divergently regulated by androgens in PCa cells, through the androgen receptor (AR), which is critical for PCa survival. AR bound to gene regulatory sites and activated the IRE1α branch, but simultaneously inhibited PERK signaling. Inhibition of the IRE1α arm profoundly reduced PCa cell growth in vitro as well as tumor formation in preclinical models of PCa in vivo. Consistently, AR and UPR gene expression were correlated in human PCa, and spliced XBP-1 expression was significantly upregulated in cancer compared with normal prostate. These data establish a genetic switch orchestrated by AR that divergently regulates the UPR pathways and suggest that targeting IRE1α signaling may have therapeutic utility in PCa.

HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network

Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. HES6 is a transcription co-factor associated with stem cell characteristics in neural tissue. Here we show that HES6 is up-regulated in aggressive human prostate cancer and drives castration-resistant tumour growth in the absence of ligand binding by enhancing the transcriptional activity of the AR, which is preferentially directed to a regulatory network enriched for transcription factors such as E2F1. In the clinical setting, we have uncovered a HES6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted by inhibition of PLK1 with restoration of sensitivity to castration. We have therefore shown for the first time the critical role of HES6 in the development of CRPC and identified its potential in patient-specific therapeutic strategies.

CSI 2264: Simultaneous Optical and Infrared Light Curves of Young Disk-bearing Stars in NGC 2264 with CoRoT and Spitzer—Evidence for Multiple Origins of Variability

We present the Coordinated Synoptic Investigation of NGC 2264, a continuous 30 day multi-wavelength photometric monitoring campaign on more than 1000 young cluster members using 16 telescopes. The unprecedented combination of multi-wavelength, high-precision, high-cadence, and long-duration data opens a new window into the time domain behavior of young stellar objects. Here we provide an overview of the observations, focusing on results from Spitzer and CoRoT. The highlight of this work is detailed analysis of 162 classical T Tauri stars for which we can probe optical and mid-infrared flux variations to 1% amplitudes and sub-hour timescales. We present a morphological variability census and then use metrics of periodicity, stochasticity, and symmetry to statistically separate the light curves into seven distinct classes, which we suggest represent different physical processes and geometric effects. We provide distributions of the characteristic timescales and amplitudes and assess the fractional representation within each class. The largest category (>20%) are optical "dippers" with discrete fading events lasting ~1-5 days. The degree of correlation between the optical and infrared light curves is positive but weak; notably, the independently assigned optical and infrared morphology classes tend to be different for the same object. Assessment of flux variation behavior with respect to (circum)stellar properties reveals correlations of variability parameters with Hα emission and with effective temperature. Overall, our results point to multiple origins of young star variability, including circumstellar obscuration events, hot spots on the star and/or disk, accretion bursts, and rapid structural changes in the inner disk. Based on data from the Spitzer and CoRoT missions. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.