Complementary Surface Characterization of Chalcopyrite by Electron Microscopy, Electron Spectroscopy, and Optical Reflectance

Surface oxidation of polished natural specimens of chalcopyrite (CuFeS2) at temperature between 23°C and 300°C in air has been characterized by Auger electron and X-ray photoelectron spectroscopies. The reaction products consisted of an outer iron oxide layer and an intermediate copper rich sulfide layer. Several different oxides and sulfides were consistent with the electron spectroscopy data, so specimens were analyzed as a function of time and temperature at selected 20 μm diameter areas with an optical microreflectometer (OMR). Since the optical properties of a compound are unique, a reflectance model with three homogeneous layers was used to calculate reflectance curves by varying the compound in and thickness of each layer. The reaction products were modelled as Cu5FeS4 in contact with the CuFeS2 and Cu2S as an intermediate layer between Cu5FeS4 and the outer oxide. The outer oxide was most consistent with Fe3O4. Relative layer thicknesses were calculated from a series of balanced chemical equations, and Cu5FeS4 was much thicker than Cu2S with total thickness increasing with increasing temperature. The total film layer thicknesses calculated at 23°C were between 10nm and 35nm. At 200°C the film thickness varied from 8nm to 51nm with greater thicknesses associated with longer reaction times. Thicknesses at 300°C ranged from 12nm to 85nm

Optical Microreflectometry and Microscopy of Chalcopyrite Specimens: Reflectance Calculation and Comparison to Backscattered Electron Microscopy

A model was developed to calculate the optical reflectance of an absorbing substrate covered by multiple thin layers of absorbing materials. Both multiple homogeneous thin layers and thin surface layers of mixed phases were modeled. Reflectance versus wavelength was measured for polished chalcopyrite (CuFeS2) and compared to calculated data. The identity and thickness of surface compounds used to calculate reflectance curves were partially determined using X-ray photoelectron and Auger electron spectroscopies. Very good agreement between theoretical and experimental reflectance curves were observed as a function of surface composition. The hue (color) and luminosity (brightness) of the polished surface were also calculated from both experimental and theoretical curves and were found to also be valuable for evaluating surface composition. Contrast in optical photomicrographs resulting from both luminosity and hue was illustrated. Secondary and backscattered electron microscopy were also used to image chalcopyrite polished surfaces which were naturally oxidized by an exposure before and after ion etching. For a substrate covered with thin layers, the resulting backscattered coefficient was calculated as a function of the backscattered coefficient for the surface and the substrate, respectively. The variations of the relative difference between the effective backscattered coefficients vs the primary beam energy exhibited a maximum for a critical thickness difference of the surface layer. The dependence of the variations in thickness of the oxidized layer with the crystallographic orientation changes of the substrate as well as the resulting contrasts of the optical and electron images were discussed

Une analyse en ondelettes par quintes

A wavelet analysis is introduced for discrete and periodic signals, which generalises to a scale ratio of 3/2 what is usually don e with a scale ratio of 2 . In this new context, we describe a fast transform algorithm similar to the one given in [l ], called T.O.R, and we show how can be considered an analogue to Mallat's algorithm .On introduit, pour des signaux discrétisés et périodisés, une analyse par ondelettes généralisant à un rapport d'échelles égal à 3/2 ce qui se pratique habituellement pour un rapport d'échelles égal à 2. On décrit dans ce nouveau contexte un algorithme de transformation rapide analogue à l'algorithme décrit dans [1] sous le nom de T.O.R et on montre comment peut également être envisagé un algorithme analogue à celui développé par Mallat

Most Lung and Colon Cancer Susceptibility Genes Are Pair-Wise Linked in Mice, Humans and Rats

Genetic predisposition controlled by susceptibility quantitative trait loci (QTLs) contributes to a large proportion of common cancers. Studies of genetics of cancer susceptibility, however, did not address systematically the relationship between susceptibility to cancers in different organs. We present five sets of data on genetic architecture of colon and lung cancer susceptibility in mice, humans and rats. They collectively show that the majority of genes for colon and lung cancer susceptibility are linked pair-wise and are likely identical or related. Four CcS/Dem recombinant congenic strains, each differing from strain BALB/cHeA by a different small random subset of ±12.5% of genes received from strain STS/A, suggestively show either extreme susceptibility or extreme resistance for both colon and lung tumors, which is unlikely if the two tumors were controlled by independent susceptibility genes. Indeed, susceptibility to lung cancer (Sluc) loci underlying the extreme susceptibility or resistance of such CcS/Dem strains, mapped in 226 (CcS-10×CcS-19)F2 mice, co-localize with susceptibility to colon cancer (Scc) loci. Analysis of additional Sluc loci that were mapped in OcB/Dem strains and Scc loci in CcS/Dem strains, respectively, shows their widespread pair-wise co-localization (P = 0.0036). Finally, the majority of published human and rat colon cancer susceptibility genes map to chromosomal regions homologous to mouse Sluc loci. 12/12 mouse Scc loci, 9/11 human and 5/7 rat colon cancer susceptibility loci are close to a Sluc locus or its homologous site, forming 21 clusters of lung and colon cancer susceptibility genes from one, two or three species. Our data shows that cancer susceptibility QTLs can have much broader biological effects than presently appreciated. It also demonstrates the power of mouse genetics to predict human susceptibility genes. Comparison of molecular mechanisms of susceptibility genes that are organ-specific and those with trans-organ effects can provide a new dimension in understanding individual cancer susceptibility

A Micro-Costing Framework for Circulating Tumor DNA Testing in Dutch Clinical Practice

Circulating tumor DNA (ctDNA) is a promising new biomarker with multiple potential applications in cancer care. Estimating total cost of ctDNA testing is necessary for reimbursement and implementation, but challenging because of variations in workflow. We aimed to develop a micro-costing framework for consistent cost calculation of ctDNA testing. First, the foundation of the framework was built, based on the complete step-wise diagnostic workflow of ctDNA testing. Second, the costing method was set up, including costs for personnel, materials, equipment, overhead, and failures. Third, the framework was evaluated by experts and applied to six case studies, including PCR-, mass spectrometry–, and next-generation sequencing–based platforms, from three Dutch hospitals. The developed ctDNA micro-costing framework includes the diagnostic workflow from blood sample collection to diagnostic test result. The framework was developed from a Dutch perspective and takes testing volume into account. An open access tool is provided to allow for laboratory-specific calculations to explore the total costs of ctDNA testing specific workflow parameters matching the setting of interest. It also allows to straightforwardly assess the impact of alternative prices or assumptions on the cost per sample by simply varying the input parameters. The case studies showed a wide range of costs, from €168 to €7638 ($199 to$9124) per sample, and generated information. These costs are sensitive to the (coverage of) platform, setting, and testing volume

Modeling Personalized Adjuvant TreaTment in EaRly stage coloN cancer (PATTERN)

Aim To develop a decision model for the population-level evaluation of strategies to improve the selection of stage II colon cancer (CC) patients who benefit from adjuvant chemotherapy. Methods A Markov cohort model with a one-month cycle length and a lifelong time horizon was developed. Five health states were included; diagnosis, 90-day mortality, death other causes, recurrence and CC death. Data from the Netherlands Cancer Registry were used to parameterize the model. Transition probabilities were estimated using parametric survival models including relevant clinical and pathological covariates. Subsequently, biomarker status was implemented using external data. Treatment effect was incorporated using pooled trial data. Model development, data sources used, parameter estimation, and internal and external validation are described in detail. To illustrate the use of the model, three example strategies were evaluated in which allocation of treatment was based on (A) 100% adherence to the Dutch guidelines, (B) observed adherence to guideline recommendations and (C) a biomarker-driven strategy. Results Overall, the model showed good internal and external validity. Age, tumor growth, tumor sidedness, evaluated lymph nodes, and biomarker status were included as covariates. For the example strategies, the model predicted 83, 87 and 77 CC deaths after 5 years in a cohort of 1000 patients for strategies A, B and C, respectively. Conclusion This model can be used to evaluate strategies for the allocation of adjuvant chemotherapy in stage II CC patients. In future studies, the model will be used to estimate population-level long-term health gain and cost-effectiveness of biomarker-based selection strategies.Financial support for this study was provided by a grant from ZonMw (Grant number: 848015007). ZonMw had no role in designing the study, interpreting the data, writing the manuscript, and publishing the report

Fusion transcripts and their genomic breakpoints in polyadenylated and ribosomal RNA-minus RNA sequencing data

BACKGROUND: Fusion genes are typically identified by RNA sequencing (RNA-seq) without elucidating the causal genomic breakpoints. However, non–poly(A)-enriched RNA-seq contains large proportions of intronic reads that also span genomic breakpoints. RESULTS: We have developed an algorithm, Dr. Disco, that searches for fusion transcripts by taking an entire reference genome into account as search space. This includes exons but also introns, intergenic regions, and sequences that do not meet splice junction motifs. Using 1,275 RNA-seq samples, we investigated to what extent genomic breakpoints can be extracted from RNA-seq data and their implications regarding poly(A)-enriched and ribosomal RNA–minus RNA-seq data. Comparison with whole-genome sequencing data revealed that most genomic breakpoints are not, or minimally, transcribed while, in contrast, the genomic breakpoints of all 32 TMPRSS2-ERG–positive tumours were present at RNA level. We also revealed tumours in which the ERG breakpoint was located before ERG, which co-existed with additional deletions and messenger RNA that incorporated intergenic cryptic exons. In breast cancer we identified rearrangement hot spots near CCND1 and in glioma near CDK4 and MDM2 and could directly associate this with increased expression. Furthermore, in all datasets we find fusions to intergenic regions, often spanning multiple cryptic exons that potentially encode neo-antigens. Thus, fusion transcripts other than classical gene-to-gene fusions are prominently present and can be identified using RNA-seq. CONCLUSION: By using the full potential of non–poly(A)-enriched RNA-seq data, sophisticated analysis can reliably identify expressed genomic breakpoints and their transcriptional effects

Presence of HIF-1 and related genes in normal mucosa, adenomas and carcinomas of the colorectum

Expression of the transcription factor hypoxia-inducible factor 1 (HIF-1), which plays a key role in cellular adaptation to hypoxia, was investigated in normal colorectal mucosa (ten), adenomas (61), and carcinomas (23). Tissue samples were analyzed for HIF-1α, its upstream regulators, von Hippel–Lindau factor, AKT, and mammalian target of rapamycin (mTOR) and its downstream targets glucose transporter 1 (GLUT1), carbonic anhydrase IX, stromal-cell-derived factor 1 (SDF-1) by immunohistochemistry. In normal colorectal mucosa, HIF-1α was observed in almost all nuclei of surface epithelial cells, probably secondary to a gradient of oxygenation, as indicated by pimonidazole staining. The same staining pattern was present in 87% of adenomas. In carcinomas, HIF-1α was present predominantly around areas of necrosis (78%). Active AKT and mTOR, were present in all adenomas, carcinomas, and in normal colorectal mucosa. GLUT1 and SDF-1 were present in the normal surface epithelium of all adenoma cases, whereas in the carcinoma GLUT1 was located around necrotic regions and SDF-1 was present in all epithelial cells. In conclusion, HIF-1α appears to be physiologically expressed in the upper part of the colorectal mucosa. The present observations support that upregulation of HIF-1α and its downstream targets GLUT1 and SDF-1 in colorectal adenomas and carcinomas may be due to hypoxia, in close interaction with an active phosphatidylinositol 3-kinases–AKT–mTOR pathway