High temperature protective coatings for refractory metals progress report no. 1, oct. 23, 1964 - jan. 23, 1965

Iridium as high temperature protective coating for unalloyed niobium and tantalu

Vibrational Properties of Nanoscale Materials: From Nanoparticles to Nanocrystalline Materials

The vibrational density of states (VDOS) of nanoclusters and nanocrystalline materials are derived from molecular-dynamics simulations using empirical tight-binding potentials. The results show that the VDOS inside nanoclusters can be understood as that of the corresponding bulk system compressed by the capillary pressure. At the surface of the nanoparticles the VDOS exhibits a strong enhancement at low energies and shows structures similar to that found near flat crystalline surfaces. For the nanocrystalline materials an increased VDOS is found at high and low phonon energies, in agreement with experimental findings. The individual VDOS contributions from the grain centers, grain boundaries, and internal surfaces show that, in the nanocrystalline materials, the VDOS enhancements are mainly caused by the grain-boundary contributions and that surface atoms play only a minor role. Although capillary pressures are also present inside the grains of nanocrystalline materials, their effect on the VDOS is different than in the cluster case which is probably due to the inter-grain coupling of the modes via the grain-boundaries.Comment: 10 pages, 7 figures, accepted for publication in Phys. Rev.

The quantitative calculation of SiC polytypes from measurements of X-ray diffraction peak intensities

An experimental determination on powder mixtures of SiC-3C and 6H polytypes using an X-ray goniometer system showed the possibility of quantitative determination of polytype fraction directly from peak intensities. In combination with calculated X-ray intensities of 15R and 4H polytype, the method yields a simple equation system for the relative quantities of SiC polytypes 15R, 6H, 4H and 3C in polycrystalline samples and powder mixtures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44679/1/10853_2004_Article_BF00551044.pd

HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade

Background: Identification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy. Methods: A research-based PAM50 assay was applied in 422 HER2-positive tumors from five II-III clinical trials (SOLTI-PAMELA, TBCRC023, TBCRC006, PER-ELISA, EGF104090). In SOLTI-PAMELA, TBCRC023, TBCRC006, and PER-ELISA, all patients had early disease and were treated with neoadjuvant lapatinib or pertuzumab plus trastuzumab for 12-24 weeks. Primary outcome was pathological complete response (pCR). In EGF104900, 296 women with advanced disease were randomized to receive either lapatinib alone or lapatinib plus trastuzumab. Progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) were evaluated. Results: A total of 305 patients with early and 117 patients with advanced HER2-positive disease were analyzed. In early disease, HER2-E represented 83.8% and 44.7% of ERBB2-high and ERBB2-low tumors, respectively. Following lapatinib and trastuzumab, the HER2-E and ERBB2 (HER2-E/ERBB2)-high group showed a higher pCR rate compared to the rest (44.5%, 95% confidence interval [CI] = 35.4% to 53.9% vs 11.6%, 95% CI = 6.9% to 18.0%; adjusted odds ratio [OR] = 6.05, 95% CI = 3.10 to 11.80, P <. 001). Similar findings were observed with neoadjuvant trastuzumab and pertuzumab (pCR rate of 66.7% in HER2-E/ERBB2-high, 95% CI = 22.3% to 95.7% vs 14.7% in others, 95% CI = 4.9% to 31.1%; adjusted OR = 11.60, 95% CI = 1.66 to 81.10, P =. 01). In the advanced setting, the HER2-E/ERBB2-high group was independently associated with longer PFS (hazard ratio [HR] = 0.52, 95% CI = 0.35 to 0.79, P <. 001); higher ORR (16.3%, 95% CI = 8.9% to 26.2% vs 3.7%, 95% CI = 0.8% to 10.3%, P =. 02); and longer OS (HR = 0.66, 95% CI = 0.44 to 0.97, P =. 01). Conclusions: Combining HER2-E subtype and ERBB2 mRNA into a single assay identifies tumors with high responsiveness to HER2-targeted therapy. This biomarker could help de-escalate chemotherapy in approximately 40% of patients with HER2-positive breast cancer

Evaluation of the third- and fourth-generation GOCE Earth gravity field models with Australian terrestrial gravity data in spherical harmonics

In March 2013 the fourth generation of ESA’s (European Space Agency) global gravity field models, DIR4 (Bruinsma et al, 2010b) and TIM4 (Pail et al, 2010), generated from the GOCE (Gravity field and steady-state Ocean Circulation Explorer) gravity observation satellite were released. We evaluate the models using an independent ground truth data set of gravity anomalies over Australia. Combined with GRACE (Gravity Recovery and Climate Experiment) satellite gravity, a new gravity model is obtained that is used to perform comparisons with GOCE models in spherical harmonics. Over Australia, the new gravity model proves to have significantly higher accuracy in the degrees below 120 as compared to EGM2008 and seems to be at least comparable to the accuracy of this model between degree 150 and degree 260. Comparisons in terms of residual quasi-geoid heights, gravity disturbances, and radial gravity gradients evaluated on the ellipsoid and at approximate GOCE mean satellite altitude (h=250 km) show both fourth generation models to improve significantly w.r.t. their predecessors.Relatively, we find a root-mean-square improvement of 39 % for the DIR4 and 23 % for TIM4 over the respective third release models at a spatial scale of 100 km (degree 200). In terms of absolute errors TIM4 is found to perform slightly better in the bands from degree 120 up to degree 160 and DIR4 is found to perform slightly better than TIM4 from degree 170 up to degree 250. Our analyses cannot confirm the DIR4 formal error of 1 cm geoid height (0.35 mGal in terms of gravity) at degree 200. The formal errors of TIM4, with 3.2 cm geoid height (0.9 mGal in terms of gravity) at degree 200, seem to be realistic. Due to combination with GRACE and SLR data, the DIR models, at satellite altitude, clearly show lower RMS values compared to TIM models in the long wavelength part of the spectrum (below degree and order 120). Our study shows different spectral sensitivity of different functionals at ground level and at GOCE satellite altitude and establishes the link among these findings and the Meissl scheme (Rummel and van Gelderen in Manuscripta Geodaetica 20:379–385, 1995)

Disruption of Retinoic Acid Receptor Alpha Reveals the Growth Promoter Face of Retinoic Acid

Retinoic acid (RA), the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs), exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-receptor alpha, RARalpha, abrogates the RA-mediated growth-inhibitory effects and unmasks the growth-promoting face of RA (Ren et al., Mol. Cell. Biol., 2005, 25:10591). The objective of this study was to investigate whether RA can differentially govern cell growth, in the presence and absence of RARalpha, through differential regulation of the "rheostat" comprising ceramide (CER), the sphingolipid with growth-inhibitory activity, and sphingosine-1-phosphate (S1P), the sphingolipid with prosurvival activity.We found that functional inhibition of endogenous RARalpha in breast cancer cells by using either RARalpha specific antagonists or a dominant negative RARalpha mutant hampers on one hand the RA-induced upregulation of neutral sphingomyelinase (nSMase)-mediated CER synthesis, and on the other hand the RA-induced downregulation of sphingosine kinase 1, SK1, pivotal for S1P synthesis. In association with RA inability to regulate the sphingolipid rheostat, cells not only survive, but also grow more in response to RA both in vitro and in vivo. By combining genetic, pharmacological and biochemical approaches, we mechanistically demonstrated that RA-induced growth is, at least in part, due to non-RAR-mediated activation of the SK1-S1P signaling.In the presence of functional RARalpha, RA inhibits cell growth by concertedly, and inversely, modulating the CER and S1P synthetic pathways. In the absence of a functional RARalpha, RA-in a non-RAR-mediated fashion-promotes cell growth by activating the prosurvival S1P signaling. These two distinct, yet integrated processes apparently concur to the growth-promoter effects of RA

Towards an International Height Reference System: insights from the Colorado geoid experiment using AUSGeoid computation methods

We apply the AUSGeoid data processing and computation methodologies to data provided for the International Height Reference System (IHRS) Colorado experiment as part of the International Association of Geodesy Joint Working Groups 0.1.2 and 2.2.2. This experiment is undertaken to test a range of different geoid computation methods from international research groups with a view to standardising these methods to form a set of conventions that can be established as an IHRS. The IHRS can realise an International Height Reference Frame to be used to study physical changes on and within the Earth. The Colorado experiment study site is much more mountainous (maximum height 4401 m) than the mostly flat Australian continent (maximum height 2228 m), and the available data over Colorado are different from Australian data (e.g. much more extensive airborne gravity coverage). Hence, we have tested and applied several modifications to the AUSGeoid approach, which had been tailored to the Australian situation. This includes different methods for the computation of terrain corrections, the gridding of terrestrial gravity data, the treatment of long-wavelength errors in the gravity anomaly grid and the combination of terrestrial and airborne data. A new method that has not previously been tested is the application of a spherical harmonic high-pass filter to residual anomalies. The results indicate that the AUSGeoid methods can successfully be used to compute a high accuracy geoid in challenging mountainous conditions. Modifications to the AUSGeoid approach lead to root-mean-square differences between geoid models up to ~ 0.028 m and agreement with GNSS-levelling data to ~ 0.044 m, but the benefits of these modifications cannot be rigorously assessed due to the limitation of the GNSS-levelling accuracy over the computation area