Using integrated data analysis to extend measurement capability (invited).

The analysis approach called integrated data analysis (IDA) provides a means to exploit all information present in multiple streams of raw data to produce the best inference of a plasma parameter. This contrasts with the typical approach in which information (data) from a single diagnostic is used to measure a given parameter, e.g., visible bremsstrahlung → Z eff. Data from a given diagnostic usually contain information on many parameters. For example, a Thomson scattering diagnostic is sensitive to bremsstrahlung and line emission in addition to electron temperature. This background light is typically subtracted off and discarded but could be used to improve knowledge of Z eff. IDA encourages explicit awareness of such information and provides the quantitative framework to exploit it. This gives IDA the ability to increase spatial and temporal resolution, increase precision and accuracy of inferences, and measure plasma parameters that are difficult or impossible to measure using single diagnostic techniques. One example is the measurement of Z eff on Madison symmetric torus using IDA since no single diagnostic can provide a robust measurement. As we enter the burning plasma era, application of IDA will be critical to the measurement of certain parameters, as diagnostic access in the harsh fusion environment will be extremely limited.

Observation of Electron Bernstein Wave Heating in a Reversed Field Pinch.

The first observation of rf heating in a reversed field pinch (RFP) using the electron Bernstein wave (EBW) is demonstrated on the Madison Symmetric Torus. Propagation across and heating in a stochastic magnetic field is observed. Novel techniques are required to measure the suprathermal electron tail generated by EBW heating in the presence of intense Ohmic heating. rf-heated electrons directly probe the edge transport properties in the RFP; measured loss rates imply a large noncollisional radial diffusivity.

Note: Effect of photodiode aluminum cathode frame on spectral sensitivity in the soft x-ray energy band.

Silicon photodiodes used for soft x-ray detection typically have a thin metal electrode partially covering the active area of the photodiode, which subtly alters the spectral sensitivity of the photodiode. As a specific example, AXUV4BST photodiodes from International Radiation Detectors have a 1.0 µm thick aluminum frame covering 19% of the active area of the photodiode, which attenuates the measured x-ray signal below ~6 keV. This effect has a small systematic impact on the electron temperature calculated from measurements of soft x-ray bremsstrahlung emission from a high-temperature plasma. Although the systematic error introduced by the aluminum frame is only a few percent in typical experimental conditions on the Madison Symmetric Torus, it may be more significant for other instruments that use similar detectors.

High-performance double-filter soft x-ray diagnostic for measurement of electron temperature structure and dynamics.

A new soft x-ray (SXR) T(e) and tomography diagnostic has been developed for MST that can be used for simultaneous SXR spectrum measurement, tomographically reconstructed emissivity, and reconstructed and line-of-sight electron temperature. The diagnostic utilizes high-performance differential transimpedance amplifiers (gain 10(5)-10(9)) to provide fast time response (up to 125 kHz), allowing for the study of plasma structure dynamics. SXR double-foil T(e) measurements are consistent with Thomson scattering. SXR brightness through a variety of filter thicknesses has been combined with charge exchange recombination spectroscopy (CHERS) impurity density measurements to determine the plasma energy spectrum. Magnetic pickup from the fluctuating magnetic fields in the plasma (B̃∼20 gauss at 10-20 kHz) has been dramatically reduced by improving the detector and housing design, so that nanoampere diode currents are now measured without interference from the substantial fluctuating magnetic field incident on the plasma facing surface of the probe.

An upgraded x-ray spectroscopy diagnostic on MST.

An upgraded x-ray spectroscopy diagnostic is used to measure the distribution of fast electrons in MST and to determine Z(eff) and the particle diffusion coefficient D(r). A radial array of 12 CdZnTe hard-x-ray detectors measures 10-150 keV Bremsstrahlung from fast electrons, a signature of reduced stochasticity and improved confinement in the plasma. A new Si soft-x-ray detector measures 2-10 keV Bremsstrahlung from thermal and fast electrons. The shaped output pulses from both detector types are digitized and the resulting waveforms are fit with Gaussians to resolve pileup and provide good time and energy resolution. Lead apertures prevent detector saturation and provide a well-known etendue, while lead shielding prevents pickup from stray x-rays. New Be vacuum windows transmit >2 keV x-rays, and additional Al and Be filters are sometimes used to reduce low energy flux for better resolution at higher energies. Measured spectra are compared to those predicted by the Fokker-Planck code CQL3D to deduce Z(eff) and D(r).

A new double-foil soft x-ray array to measure T(e) on the MST reversed field pinch.

A soft x-ray (SXR) diagnostic to measure electron temperature on the Madison Symmetric Torus using two complementary methods is presented. Both methods are based on the double-foil technique, which calculates electron temperature via the ratio of SXR bremsstrahlung emission from the plasma in two different energy ranges. The tomographic emissivity method applies the double-foil technique to a tomographic reconstruction of SXR emissivity, creating a two-dimensional map of temperature throughout the plasma. In contrast, the direct brightness method applies the double-foil technique directly to the measured brightness and generates vertical and horizontal radial profiles. Extensive modeling demonstrates advantages and limitations in both techniques. For example, although the emissivity technique provides a two-dimensional mapping of temperature, its reliance on multiple tomographic inversions introduces some artifacts into the results. On the other hand, the more direct brightness technique avoids these artifacts but is only able to provide a radial profile of electron temperature.

Frequent requirement of hedgehog signaling in non-small cell lung carcinoma.

Although it had previously been suggested that the hedgehog (HH) pathway might be activated in some lung tumors, the dependence of non-small cell lung carcinomas (NSCLC) for HH activity had not been comprehensively studied. During a screen of a panel of 60 human tumor cell lines with an HH antagonist, we observed that the proliferation of a subset of NSCLC cell lines was inhibited. These NSCLC cell lines express HH, as well as key HH target genes, consistent with them being activated through an autocrine mechanism. Interestingly, we also identified a number of NSCLC cell lines that express high levels of the downstream transcription factor GLI1 and harbor enhanced levels of HH activity, but appear insensitive to known HH antagonists. We hypothesized that the high levels of GLI1 in these cells would function downstream of the HH antagonist target, allowing them to bypass the antagonist-mediated block in proliferation. Consistent with this hypothesis, when the levels of GLI1 are knocked down in such cells, they become sensitive to these inhibitors. We go on to show that a large percentage of primary NSCLC samples express GLI1, consistent with constitutive activation of the HH pathway in these samples. Taken together, these results establish the involvement of the HH signaling pathway in a subset of NSCLCs.

A freely diffusible form of Sonic hedgehog mediates long-range signalling.

The secreted protein Sonic hedgehog (Shh) exerts many of its patterning effects through a combination of short- and long-range signalling. Three distinct mechanisms, which are not necessarily mutually exclusive, have been proposed to account for the long-range effects of Shh: simple diffusion of Shh, a relay mechanism in which Shh activates secondary signals, and direct delivery of Shh through cytoplasmic extensions, termed cytonemes. Although there is much data (using soluble recombinant Shh (ShhN)) to support the simple diffusion model of long-range Shh signalling, there has been little evidence to date for a native form of Shh that is freely diffusible and not membrane-associated. Here we provide evidence for a freely diffusible form of Shh (s-ShhNp) that is cholesterol modified, multimeric and biologically potent. We further demonstrate that the availability of s-ShhNp is regulated by two functional antagonists of the Shh pathway, Patched (Ptc) and Hedgehog-interacting protein (Hip). Finally, we show a gradient of s-ShhNp across the anterior-posterior axis of the chick limb, demonstrating the physiological relevance of s-ShhNp.