Validation of biomarkers predictive of tumor location in coloadenocarcinoma, an analysis of the TCGA COAD dataset

Tumor localization correlates with prognosis in coloadenocarcinoma, with aboral tumors having a better overall survival. This can be attributed to their better response to biologicals such as the anti-EGFR (epidermal growth factor receptor) cetuximab. Since the localization of a tumor is trivially determined in a clinical setting, it remains a valuable surrogate parameter for predicting patient outcomes, though it is not a mechanistic explanation. Some possible explanations have been offered: it could be that aboral colonic epithelial cells respond differently to mutagenic stimuli, or that the variation in gut flora from adoral to aboral plays a role in tumor development or behavior. So far, there has been no consensus. By eliminating tumor localization as a confounder, since some aboral tumors behave and develop more like adoral tumors and vice versa, better treatment decisions would be possible. While being slightly more complicated than simply defining the tumor location, testing for a handful of mutations in a tumor specimen is a routine procedure and the increased predictive power of such a model would be of great value for making difficult treatment decisions. It would also represent a starting point for better understanding possible underlying molecular mechanisms. It was hypothesized that –regardless of the causal relationships– this “sidedness” of coloadenocarcinomas could be reconstructed on a genomic and transcriptomic level. In order to test this hypothesis, data from the TCGA (Tumor Cancer Genome Atlas) database was used in a case-control study design to create expression profiles by training two distinct machine-learning algorithms to predict tumor location. The algorithms identified PRAC1, HOXB13, HOXC9, HOXC6, HOTAIR, PRAC2, and HOXC8 (all members of the homeobox gene family) as well as BST2, PLTP, FN1, ITLN1, and AREG as predictors of localization. These finding corroborate previous research using various other methods and fit well into the established framework of previously published literature which solidifies the veracity of the machine-learning models as implemented. As an additional benefit, the work-flow for creating the genomic and transcrip- tomic profiles is very flexible and can be used for further analysis of the TCGA dataset.Tumorlokalisation korreliert mit der Prognose Koloadenokarzinome, wobei ab- orale Tumore ein besseres Gesamtüberleben zeigen. Dies kann man auf deren bessere Antwort auf Biologika, wie das anti-EGFR (epidermal growth factor receptor) Medikament Cetuximab, zurückführen. Da die Lokalisation eines Tumors im klinischen Alltag vergleichsweise unkom- pliziert festgestellt werden kann ist sie nach wie vor ein wichtiger Surrogatpa- rameter für die Vorhersage von Therapieerfolg, obwohl sie keine mechanistische Erklärung ist. Einige mögliche Erklärungen wurden schon vorgeschlagen: es könnte sein, dass die aborale Kolonepithelzellen anders auf mutagene Stimuli reagieren, oder dass die Variation der Flora im Kolon von adoral nach aboral eine Rolle in der Tumorentwicklung und des Verhaltens spielt. Leider gibt es noch keinen Konsens. Die Hypothese wurde aufgestellt, dass –unabhängig von den kausalen Zusammenhängen– diese “Seitigkeit” der Koloadenokarzinomen auf genomischer und transkriptomischer Ebene rekonstruiert werden kann. Indem man die Tumorlokalisation als Confounder eliminiert könnten Therapieentschei- dungen besser getroffen werden, da sich manche aborale Tumoren wie adorale Tumore entwickeln und verhalten, und umgekehrt. Obwohl etwas komplizierter als nur Tumorlokalisation zu bestimmen, ist die Suche nach einer Handvoll Muta- tionen in einer Tumorprobe ein klinisches Routineverfahren und die verbesserte Vorhersagekraft eines solchen Modells wäre wertvoll für schwierige Behand- lungsentscheidungen. Es wäre auch ein Startpunkt für weitere Untersuchungen, um die zugrundeliegenden molekularen Mechanismen besser zu verstehen. Die Hypothese wurde aufgestellt, dass die “Seitigkeit” der Koloadenokarzinome auf genomischer und transcriptomischer Ebene rekonstruiert werden könnte. Um die Hypothese zu überprüfen wurden Daten aus der TCGA (Tumor Cancer Genome Atlas) Datenbank in einer Fall-Kontroll-Studie verwendet, um Expres- sionsprofile mittels Machine-Learning-Algorithmen zu erarbeiten, welche die Tumorlokalisation vorhersagen können. Die Algorithmen identifizierten sowohl PRAC1, HOXB13, HOXC9, HOXC6, HOTAIR, PRAC2, und HOXC8 (alles Mitglieder der Homeobox Genfamilie) als auch BST2, PLTP, FN1, ITLN1, und AREG als Prediktoren der Tumorlokalisation. Diese Ergebnisse bestäti- gen bereits publizierte Erkenntnisse und bekräftigen somit die Genauigkeit der Machine-Learning-Algorithmen wie sie hier implementiert wurden. Als zusätzlicher Nutzen ist der Workflow für die Erarbeitung der genomischen und transcriptomischen Profile sehr flexibel und kann für weitere Analysen der TCGA Daten verwendet werden

Retrieval analysis of different orthodontic brackets: the applicability of electron microprobe techniques for determining material heterogeneities and corrosive potential

OBJECTIVE: The objective of this study was to investigate the applicability of micro-analytical methods with high spatial resolution to the characterization of the composition and corrosion behavior of two bracket systems. MATERIAL AND METHODS: The surfaces of six nickel-free brackets and six nickel-containing brackets were examined for signs of corrosion and qualitative surface analysis using an electron probe microanalyzer (EPMA), prior to bonding to patient's tooth surfaces and four months after clinical use. The surfaces were characterized qualitatively by secondary electron (SE) images and back scattered electron (BSE) images in both compositional and topographical mode. Qualitative and quantitative wavelength-dispersive analyses were performed for different elements, and by utilizing qualitative analysis the relative concentration of selected elements was mapped two-dimensionally. The absolute concentration of the elements was determined in specially prepared brackets by quantitative analysis using pure element standards for calibration and calculating correction-factors (ZAF). RESULTS: Clear differences were observed between the different bracket types. The nickel-containing stainless steel brackets consist of two separate pieces joined by a brazing alloy. Compositional analysis revealed two different alloy compositions, and reaction zones on both sides of the brazing alloy. The nickel-free bracket was a single piece with only slight variation in element concentration, but had a significantly rougher surface. After clinical use, no corrosive phenomena were detectable with the methods applied. Traces of intraoral wear at the contact areas between the bracket slot and the arch wire were verified. CONCLUSION: Electron probe microanalysis is a valuable tool for the characterization of element distribution and quantitative analysis for corrosion studies

Outgassing of Ordinary Chondritic Material and Some of its Implications for the Chemistry of Asteroids, Planets, and Satellites

We used chemical equilibrium calculations to model thermal outgassing of ordinary chondritic material as a function of temperature, pressure, and bulk compositions and use our results to discuss outgassing on asteroids and the early Earth. The calculations include ~1,000 solids and gases of the elements Al, C, Ca, Cl, Co, Cr, F, Fe, H, K, Mg, Mn, N, Na, Ni, O, P, S, Si, and Ti. The major outgassed volatiles from ordinary chondritic material are CH4, H2, H2O, N2, and NH3(the latter at conditions where hydrous minerals form). Contrary to widely held assumptions, CO is never the major C-bearing gas during ordinary chondrite metamorphism. The calculated oxygen fugacity (partial pressure) of ordinary chondritic material is close to that of the quartz-fayalite-iron (QFI) buffer. Our results are insensitive to variable total pressure, variable volatile element abundances, and kinetic inhibition of C and N dissolution in Fe metal. Our results predict that Earth's early atmosphere contained CH4, H2, H2O, N2, and NH3; similar to that used in Miller-Urey synthesis of organic compounds.Comment: 72 pages, 17 figures, 3 tables; submitted to Icaru

Uniformly coated highly porous graphene/MnO2 foams for flexible asymmetric supercapacitors

Supercapacitors are called to play a prominent role in the newly emerging markets of electric vehicles, flexible displays and sensors, and wearable electronics. In order to compete with current battery technology, supercapacitors have to be designed with highly conductive current collectors exhibiting high surface area per unit volume and uniformly coated with pseudocapacitive materials, which is crucial to boost the energy density while maintaining a high power density. Here, we present a versatile technique to prepare thickness-controlled thin-film micro graphene foams (μGFs) with pores in the lower micrometer range grown by chemical vapor deposition which can be used as highly conductive current collectors in flexible supercapacitors. To fabricate the μGF, we use porous metallic catalytic substrates consisting of nickel/copper alloy synthesized on nickel foil by electrodeposition in an electrolytic solution. Changing the duration of the electrodeposition allows the control of the thickness of the metal foam, and thus of the μGF, ranging from a few micrometers to the millimeter scale. The resulting μGF with a thickness and pores in the micrometer regime exhibits high structural quality which leads to a very low intrinsic resistance of the devices. Transferred onto flexible substrates, we demonstrate a uniform coating of the μGFs with manganese oxide, a pseudocapacitively active material. Considering the porous structure and the thickness of the μGFs, square wave potential pulses are used to ensure uniform coverage by the oxide material boosting the volumetric and areal capacitance to 14 F cm and 0.16 F cm. The μGF with a thickness and pores in the micrometer regime in combination with a coating technique tuned to the porosity of the μGF is of great relevance for the development of supercapacitors based on state-of-the-art graphene foams

Variação sazonal na captura de lula (Doryteuthis piei Blainville, 1823) no sudeste do Brasil, utilizando atração luminosa e rede corrediça

At the Maritime Fishery Division of the Fishery Institute of the São Paulo State Secretaria da Agricultura, Brazil, from 1981 to 1985, it was verified, between the latitudes 23° 11'S and 27° 17'S, till 50 miles off - shore that squid fishery increased mostly in terms of weight in Summer, followed by Autum, Winter and Spring, decreesingly. Nunber of individuals was greater in Autinn, followed by Sunmer, Winter and the Spring. Catches happened in 40% of fishing days. The probability of finding these animals remained the same all year round. Squids were attracted by ligth and caught in a sliding net.Em trabalho realizado entre as latitudes 23°11'S e 27°17'S, até o limite de 50 milhas náuticas a leste, de 1981 a 1985, utilizando atração luminosa e rede corrediça, verificou-se que a captura em peso de lula (Doryteuthis piei Blainville, 1823) foi maior no verão, seguida do outono, inverno e primavera. 0 número de indivíduos foi maior no outono, seguido do verão, inverno e primavera. As capturas ocorreram em 40% dos dias de pesca. A probabilidade de encontrar-se o pescado é sempre a mesma, em qualquer das estaçõesdo ano

On the iron isotope composition of Mars and volatile depletion in the terrestrial planets

Iron is the most abundant multivalent element in planetary reservoirs, meaning its isotope composition (expressed as δ57Fe) may record signatures of processes that occurred during the formation and subsequent differentiation of the terrestrial planets. Chondritic meteorites, putative constituents of the planets and remnants of undifferentiated inner solar system bodies, have δ57Fe ≈ 0‰; an isotopic signature shared with the Martian Shergottite–Nakhlite–Chassignite (SNC) suite of meteorites. The silicate Earth and Moon, as represented by basaltic rocks, are distinctly heavier, δ57Fe≈+0.1‰. However, some authors have recently argued, on the basis of iron isotope measurements of abyssal peridotites, that the composition of the Earth’s mantle is δ57Fe = +0.04 ± 0.04‰, indistinguishable from the mean Martian value. To provide a more robust estimate for Mars, we present new high-precision iron isotope data on 17 SNC meteorites and 5 mineral separates. We find that the iron isotope compositions of Martian meteorites reflect igneous processes, with nakhlites and evolved shergottites displaying heavier δ57Fe(+0.05 ± 0.03‰), whereas MgO-rich rocks are lighter (δ57Fe≈−0.01 ±0.02‰). These systematics are controlled by the fractionation of olivine and pyroxene, attested to by the lighter isotope composition of pyroxene compared to whole rock nakhlites. Extrapolation of the δ57Fe SNC liquid line of descent to a putative Martian mantle yields a δ57Fe value lighter than its terrestrial counterpart, but indistinguishable from chondrites. Iron isotopes in planetary basalts of the inner solar system correlate positively with Fe/Mn and silicon isotopes. While Mars and IV-Vesta are undepleted in iron and accordingly have chondritic δ57Fe, the Earth experienced volatile depletion at low (1300 K) temperatures, likely at an early stage in the solar nebula, whereas additional post-nebular Fe loss is possible for the Moon and angrites

Retrieval analysis of different orthodontic brackets: the applicability of electron microprobe techniques for determining material heterogeneities and corrosive potential

OBJECTIVE: The objective of this study was to investigate the applicability of micro-analytical methods with high spatial resolution to the characterization of the composition and corrosion behavior of two bracket systems. MATERIAL AND METHODS: The surfaces of six nickel-free brackets and six nickel-containing brackets were examined for signs of corrosion and qualitative surface analysis using an electron probe microanalyzer (EPMA), prior to bonding to patient's tooth surfaces and four months after clinical use. The surfaces were characterized qualitatively by secondary electron (SE) images and back scattered electron (BSE) images in both compositional and topographical mode. Qualitative and quantitative wavelength-dispersive analyses were performed for different elements, and by utilizing qualitative analysis the relative concentration of selected elements was mapped two-dimensionally. The absolute concentration of the elements was determined in specially prepared brackets by quantitative analysis using pure element standards for calibration and calculating correction-factors (ZAF). RESULTS: Clear differences were observed between the different bracket types. The nickel-containing stainless steel brackets consist of two separate pieces joined by a brazing alloy. Compositional analysis revealed two different alloy compositions, and reaction zones on both sides of the brazing alloy. The nickel-free bracket was a single piece with only slight variation in element concentration, but had a significantly rougher surface. After clinical use, no corrosive phenomena were detectable with the methods applied. Traces of intraoral wear at the contact areas between the bracket slot and the arch wire were verified. CONCLUSION: Electron probe microanalysis is a valuable tool for the characterization of element distribution and quantitative analysis for corrosion studies