Oxidation Through Coating Cracks of SiC-Protected Carbon/Carbon

The oxidation of SiC-protected carbon/carbon through machined slots and naturally occurring craze cracks in the SiC was studied. The slot and crack geometries were characterized, and the subsurface oxidation of the carbon/carbon substrate at temperatures of 1000 to 1300 C in air was assessed using weight change, x-ray computed tomography, and optical microscopy of sections. Rate constants were derived from these measurements and compared with a two-step diffusion control model of carbon oxidation. Oxidation kinetic measurements on both the specimens with machined slots and with naturally occurring craze cracks showed good agreement with the model

Terahertz Computed Tomography of NASA Thermal Protection System Materials

A terahertz axial computed tomography system has been developed that uses time domain measurements in order to form cross-sectional image slices and three-dimensional volume renderings of terahertz-transparent materials. The system can inspect samples as large as 0.0283 cubic meters (1 cubic foot) with no safety concerns as for x-ray computed tomography. In this study, the system is evaluated for its ability to detect and characterize flat bottom holes, drilled holes, and embedded voids in foam materials utilized as thermal protection on the external fuel tanks for the Space Shuttle. X-ray micro-computed tomography was also performed on the samples to compare against the terahertz computed tomography results and better define embedded voids. Limits of detectability based on depth and size for the samples used in this study are loosely defined. Image sharpness and morphology characterization ability for terahertz computed tomography are qualitatively described

Oxidation of Carbon/Carbon through Coating Cracks

Reinforced carbon/carbon (RCC) is used to protect the wing leading edge and nose cap of the Space Shuttle Orbiter on re-entry. It is composed of a lay-up of carbon/carbon fabric protected by a SiC conversion coating. Due to the thermal expansion mismatch of the carbon/carbon and the SiC, the SiC cracks on cool-down from the processing temperature. The cracks act as pathways for oxidation of the carbon/carbon. A model for the diffusion controlled oxidation of carbon/carbon through machined slots and cracks is developed and compared to laboratory experiments. A symmetric cylindrical oxidation cavity develops under the slots, confirming diffusion control. Comparison of cross sectional dimensions as a function of oxidation time shows good agreement with the model. A second set of oxidation experiments was done with samples with only the natural craze cracks, using weight loss as an index of oxidation. The agreement of these rates with the model is quite reasona

NDE for Characterizing Oxidation Damage in Reinforced Carbon-Carbon

In this study, coated reinforced carbon-carbon (RCC) samples of similar structure and composition as that from the NASA space shuttle orbiter s thermal protection system were fabricated with slots in their coating simulating craze cracks. These specimens were used to study oxidation damage detection and characterization using NDE methods. These specimens were heat treated in air at 1143 and 1200 C to create cavities in the carbon substrate underneath the coating as oxygen reacted with the carbon and resulted in its consumption. The cavities varied in diameter from approximately 1 to 3 mm. Single-sided NDE methods were used since they might be practical for on-wing inspection, while x-ray micro-computed tomography (CT) was used to measure cavity sizes in order to validate oxidation models under development for carbon-carbon materials. An RCC sample having a naturally-cracked coating and subsequent oxidation damage was also studied with x-ray micro-CT. This effort is a follow-on study to one that characterized NDE methods for assessing oxidation damage in an RCC sample with drilled holes in the coating. The results of that study are briefly reviewed in this article as well. Additionally, a short discussion on the future role of simulation to aid in these studies is provided

Oxidation Through Coating Cracks of SiC-Protected Carbon/Carbon

The oxidation of SiC-protected carbon/carbon through machined slots and naturally occurring craze cracks in the SiC was studied. The slot and crack geometries were characterized, and the subsurface oxidation of the carbon/carbon substrate at temperatures of 1000 to 1300 C in air was assessed using weight change, x-ray computed tomography, and optical microscopy of sections. Rate constants were derived from these measurements and compared with a two-step diffusion control model of carbon oxidation. Oxidation kinetic measurements on both the specimens with machined slots and with naturally occurring craze cracks showed good agreement with the model

Nondestructive Evaluation (NDE) for Characterizing Oxidation Damage in Cracked Reinforced Carbon-Carbon

In this study, coated reinforced carbon-carbon (RCC) samples of similar structure and composition as that from the NASA space shuttle orbiter's thermal protection system were fabricated with slots in their coating simulating craze cracks. These specimens were used to study oxidation damage detection and characterization using nondestructive evaluation (NDE) methods. These specimens were heat treated in air at 1143 C and 1200 C to create cavities in the carbon substrate underneath the coating as oxygen reacted with the carbon and resulted in its consumption. The cavities varied in diameter from approximately 1 to 3mm. Single-sided NDE methods were used because they might be practical for on-wing inspection, while X-ray micro-computed tomography (CT) was used to measure cavity sizes in order to validate oxidation models under development for carbon-carbon materials. An RCC sample having a naturally cracked coating and subsequent oxidation damage was also studied with X-ray micro-CT. This effort is a follow-on study to one that characterized NDE methods for assessing oxidation damage in an RCC sample with drilled holes in the coating

Earth system science frontiers - an early career perspective

The exigencies of the global community toward Earth system science will increase in the future as the human population, economies, and the human footprint on the planet continue to grow. This growth, combined with intensifying urbanization, will inevitably exert increasing pressure on all ecosystem services. A unified interdisciplinary approach to Earth system science is required that can address this challenge, integrate technical demands and long-term visions, and reconcile user demands with scientific feasibility. Together with the research arms of the World Meteorological Organization, the Young Earth System Scientists community has gathered early-career scientists from around the world to initiate a discussion about frontiers of Earth system science. To provide optimal information for society, Earth system science has to provide a comprehensive understanding of the physical processes that drive the Earth system and anthropogenic influences. This understanding will be reflected in seamless prediction systems for environmental processes that are robust and instructive to local users on all scales. Such prediction systems require improved physical process understanding, more high-resolution global observations, and advanced modeling capability, as well as high-performance computing on unprecedented scales. At the same time, the robustness and usability of such prediction systems also depend on deepening our understanding of the entire Earth system and improved communication between end users and researchers. Earth system science is the fundamental baseline for understanding the Earth’s capacity to accommodate humanity, and it provides a means to have a rational discussion about the consequences and limits of anthropogenic influence on Earth. Without its progress, truly sustainable development will be impossible. © 2017 American Meteorological Society. For information regarding reuse of this content and general copyright information, consult the AMS Copyright Policy (www.ametsoc.org/PUBSReuseLicenses)

Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

<p>Abstract</p> <p>Background</p> <p>The activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab combined with oxaliplatin/leucovorin/5-fluorouracil (FUFOX) was assessed in first-line metastatic gastric and oesophago-gastric junction (OGJ) cancer in a prospective phase II study showing a promising objective tumour response rate of 65% and a low mutation frequency of <it>KRAS </it>(3%). The aim of the correlative tumour tissue studies was to investigate the relationship between <it>EGFR </it>gene copy numbers, activation of the EGFR pathway, expression and mutation of E-cadherin, V600E BRAF mutation and clinical outcome of patients with gastric and OGJ cancer treated with cetuximab combined with FUFOX.</p> <p>Methods</p> <p>Patients included in this correlative study (<it>n </it>= 39) were a subset of patients from the clinical phase II study. The association between <it>EGFR </it>gene copy number, activation of the EGFR pathway, abundance and mutation of E-cadherin which plays an important role in these disorders, BRAF mutation and clinical outcome of patients was studied. <it>EGFR </it>gene copy number was assessed by FISH. Expression of the phosphorylated forms of EGFR and its downstream effectors Akt and MAPK, in addition to E-cadherin was analysed by immunohistochemistry. The frequency of mutant V600E BRAF was evaluated by allele-specific PCR and the mutation profile of the E-cadherin gene <it>CDH1 </it>was examined by DHPLC followed by direct sequence analysis. Correlations with overall survival (OS), time to progression (TTP) and overall response rate (ORR) were assessed.</p> <p>Results</p> <p>Our study showed a significant association between increased <it>EGFR </it>gene copy number (≥ 4.0) and OS in gastric and OGJ cancer, indicating the possibility that patients may be selected for treatment on a genetic basis. Furthermore, a significant correlation was shown between activated EGFR and shorter TTP and ORR, but not between activated EGFR and OS. No V600E BRAF mutations were identified. On the other hand, an interesting trend between high E-cadherin expression levels and better OS was observed and two <it>CDH1 </it>exon 9 missense mutations (A408V and D402H) were detected.</p> <p>Conclusion</p> <p>Our finding that increased <it>EGFR </it>gene copy numbers, activated EGFR and the E-cadherin status are potentially interesting biomarkers needs to be confirmed in larger randomized clinical trials.</p> <p>Trial registration</p> <p>Multicentre clinical study with the European Clinical Trials Database number 2004-004024-12.</p

Identification of Hypoxia-Regulated Proteins Using MALDI-Mass Spectrometry Imaging Combined with Quantitative Proteomics

Hypoxia is present in most solid tumors and is clinically correlated with increased metastasis and poor patient survival. While studies have demonstrated the role of hypoxia and hypoxia-regulated proteins in cancer progression, no attempts have been made to identify hypoxia-regulated proteins using quantitative proteomics combined with MALDI-mass spectrometry imaging (MALDI-MSI). Here we present a comprehensive hypoxic proteome study and are the first to investigate changes in situ using tumor samples. In vitro quantitative mass spectrometry analysis of the hypoxic proteome was performed on breast cancer cells using stable isotope labeling with amino acids in cell culture (SILAC). MS analyses were performed on laser-capture microdissected samples isolated from normoxic and hypoxic regions from tumors derived from the same cells used in vitro. MALDI-MSI was used in combination to investigate hypoxia-regulated protein localization within tumor sections. Here we identified more than 100 proteins, both novel and previously reported, that were associated with hypoxia. Several proteins were localized in hypoxic regions, as identified by MALDI-MSI. Visualization and data extrapolation methods for the in vitro SILAC data were also developed, and computational mapping of MALDI-MSI data to IHC results was applied for data validation. The results and limitations of the methodologies described are discussed. 2014 American Chemical Societ

Pharmacogenomic and structural analysis of constitutive G-protein coupled receptor activity

Premi a l'excel·lència investigadora. Àmbit de les Ciències de la Salut. 2008G-protein coupled receptors (GPCRs) respond to a chemically diverse plethora of signal transduction molecules. The notion that GPCRs also signal without an external chemical trigger, i.e. in a constitutive or spontaneous manner, resulted in a paradigm shift in the field of GPCR pharmacology. With the recognition of constitutive GPCR activity and the fact that GPCR binding and signaling can be strongly affected by a single point mutation, GPCR pharmacogenomics obtained a lot of attention. For a variety of GPCRs, point mutations have been convincingly linked to human disease. Mutations within conserved motifs, known to be involved in GPCR activation, might explain the properties of some naturally occurring constitutively active GPCR variants linked to disease. A brief history historical introduction to the present concept of constitutive receptor activity is given and the pharmacogenomic and the structural aspects of constitutive receptor activity are described