Palaeotsunami imprints in the near-coast sedimentary records of the Gulfs of Lakonia and Argolis (Peloponnese, Greece)

From historical accounts it is well-known that the coasts of the Gulfs of Lakonia and Argolis (southern and eastern Peloponnese, Greece) have been repeatedly affected by tsunamis during historical times. It is assumed that these palaeotsunamis left sedimentological and geomorphological traces in the geological record which are still detectable these days. As both gulfs are located within one of the seismically most active regions in whole western Eurasia in particular the nearby Hellenic Trench is regarded as the main trigger for tsunami generation. Against this background, selected near-coast sedimentary archives were studied by means of sedimentological, geomorphological, geophysical, geochemical and microfaunal investigations in order to detect signatures of Holocene palaeotsunamigenic activity. The investigations revealed allochthonous sediment layers featuring distinctive sedimentary characteristics of marine high-energy event deposits in most of the investigated study areas. In order to differentiate between the geomorphodynamic driving mechanisms for the deposition of the associated marine high-energy event layers, a multi-method approach was used. The detected high-energy marine deposits are suggested to be of tsunamigenic origin. Radiocarbon dating results allowed establishing local event geo-chronostratigraphies and correlations on a local and regional scale as well as correlations with already described palaeotsunami findings on a supra-regional scale. The geochronological dataset attests repeated tsunamigenic activity at least since the 5th millennium BC up to the 17th century AD. For the studied areas in southeastern Lakonia up to four palaeotsunami event generations were identified, for central Lakonia three and for the investigated areas around the Argolis Gulf also up to four. Comparing the findings with literature data, chronological correlations were found with palaeotsunami deposits detected in near-coast geological archives of Akarnania, of the southwestern, the western and northwestern Peloponnese, with event deposits found on Crete and on the Ionian Islands of Cefalonia and Lefkada as well as with findings from southeastern Sicily (Italy) and Cesarea (Israel). By the identification of multiple palaeotsunami event layers, disturbing autochthonous near-coast sedimentary records of the Gulfs of Lakonia and Argolis during the last seven millennia, a significant tsunami frequency is attested for these regions.

High precision tools for slepton pair production processes at hadron colliders

In this thesis, we develop high precision tools for the simulation of slepton pair production processes at hadron colliders and apply them to phenomenological studies at the LHC. Our approach is based on the POWHEG method for the matching of next-to-leading order results in perturbation theory to parton showers. We calculate matrix elements for slepton pair production and for the production of a slepton pair in association with a jet perturbatively at next-to-leading order in supersymmetric quantum chromodynamics. Both processes are subsequently implemented in the POWHEG BOX, a publicly available software tool that contains general parts of the POWHEG matching scheme. We investigate phenomenological consequences of our calculations in several setups that respect experimental exclusion limits for supersymmetric particles and provide precise predictions for slepton signatures at the LHC. The inclusion of QCD emissions in the partonic matrix elements allows for an accurate description of hard jets. Interfacing our codes to the multi-purpose Monte-Carlo event generator PYTHIA, we simulate parton showers and slepton decays in fully exclusive events. Advanced kinematical variables and specific search strategies are examined as means for slepton discovery in experimentally challenging setups.

Species specific nitrogen isotope analysis by NanoSIMS

Der atmosphärische Kreislauf reaktiver Stickstoffverbindungen beschäftigt sowohl die Naturwissenschaftler als auch die Politik. Dies ist insbesondere darauf zurückzuführen, dass reaktive Stickoxide die Bildung von bodennahem Ozon kontrollieren. Reaktive Stickstoffverbindungen spielen darüber hinaus als gasförmige Vorläufer von Feinstaubpartikeln eine wichtige Rolle und der Transport von reaktivem Stickstoff über lange Distanzen verändert den biogeochemischen Kohlenstoffkreislauf des Planeten, indem er entlegene Ökosysteme mit Stickstoff düngt. Die Messungen von stabilen Stickstoffisotopenverhältnissen (15N/14N) bietet ein Hilfsmittel, welches es erlaubt, die Quellen von reaktiven Stickstoffverbindungen zu identifizieren und die am Stickstoffkeislauf beteiligten Reaktionen mithilfe ihrer reaktionsspezifischen Isotopenfraktionierung genauer zu untersuchen. rnIn dieser Doktorarbeit demonstriere ich, dass es möglich ist, mit Hilfe von Nano-Sekundärionenmassenspektrometrie (NanoSIMS) verschiedene stickstoffhaltige Verbindungen, die üblicherweise in atmosphärischen Feinstaubpartikeln vorkommen, mit einer räumlichen Auflösung von weniger als einem Mikrometer zu analysieren und zu identifizieren. Die Unterscheidung verschiedener stickstoffhaltiger Verbindungen erfolgt anhand der relativen Signalintensitäten der positiven und negativen Sekundärionensignale, die beobachtet werden, wenn die Feinstaubproben mit einem Cs+ oder O- Primärionenstrahl beschossen werden. Die Feinstaubproben können direkt auf dem Probenahmesubstrat in das Massenspektrometer eingeführt werden, ohne chemisch oder physikalisch aufbereited zu werden. Die Methode wurde Mithilfe von Nitrat, Nitrit, Ammoniumsulfat, Harnstoff, Aminosären, biologischen Feinstaubproben (Pilzsporen) und Imidazol getestet. Ich habe gezeigt, dass NO2 Sekundärionen nur beim Beschuss von Nitrat und Nitrit (Salzen) mit positiven Primärionen entstehen, während NH4+ Sekundärionen nur beim Beschuss von Aminosäuren, Harnstoff und Ammoniumsalzen mit positiven Primärionen freigesetzt werden, nicht aber beim Beschuss biologischer Proben wie z.B. Pilzsporen. CN- Sekundärionen werden beim Beschuss aller stickstoffhaltigen Verbindungen mit positiven Primärionen beobachtet, da fast alle Proben oberflächennah mit Kohlenstoffspuren kontaminiert sind. Die relative Signalintensität der CN- Sekundärionen ist bei kohlenstoffhaltigen organischen Stickstoffverbindungen am höchsten.rnDarüber hinaus habe ich gezeigt, dass an reinen Nitratsalzproben (NaNO3 und KNO3), welche auf Goldfolien aufgebracht wurden speziesspezifische stabile Stickstoffisotopenverhältnisse mithilfe des 15N16O2- / 14N16O2- - Sekundärionenverhältnisses genau und richtig gemessen werden können. Die Messgenauigkeit auf Feldern mit einer Rastergröße von 5×5 µm2 wurde anhand von Langzeitmessungen an einem hausinternen NaNO3 Standard als ± 0.6 ‰ bestimmt. Die Differenz der matrixspezifischen instrumentellen Massenfraktionierung zwischen NaNO3 und KNO3 betrug 7.1 ± 0.9 ‰. 23Na12C2- Sekundärionen können eine ernst zu nehmende Interferenz darstellen wenn 15N16O2- Sekundärionen zur Messung des nitratspezifischen schweren Stickstoffs eingesetzt werden sollen und Natrium und Kohlenstoff im selben Feinstaubpartikel als interne Mischung vorliegt oder die natriumhaltige Probe auf einem kohlenstoffhaltigen Substrat abgelegt wurde. Selbst wenn, wie im Fall von KNO3, keine derartige Interferenz vorliegt, führt eine interne Mischung mit Kohlenstoff im selben Feinstaubpartikel zu einer matrixspezifischen instrumentellen Massenfraktionierung die mit der folgenden Gleichung beschrieben werden kann: 15Nbias = (101 ± 4) ∙ f − (101 ± 3) ‰, mit f = 14N16O2- / (14N16O2- + 12C14N-). rnWird das 12C15N- / 12C14N- Sekundärionenverhältnis zur Messung der stabilen Stickstoffisotopenzusammensetzung verwendet, beeinflusst die Probematrix die Messungsergebnisse nicht, auch wenn Stickstoff und Kohlenstoff in den Feinstaubpartikeln in variablen N/C–Verhältnissen vorliegen. Auch Interferenzen spielen keine Rolle. Um sicherzustellen, dass die Messung weiterhin spezifisch auf Nitratspezies eingeschränkt bleibt, kann eine 14N16O2- Maske bei der Datenauswertung verwendet werden. Werden die Proben auf einem kohlenstoffhaltigen, stickstofffreien Probennahmesubstrat gesammelt, erhöht dies die Signalintensität für reine Nitrat-Feinstaubpartikel.

Hierarchical clustering of flow cytometry data for the study of conventional central chondrosarcoma

We have investigated the use of hierarchical clustering of flow cytometry data to classify samples of conventional central chondrosarcoma, a malignant cartilage forming tumor of uncertain cellular origin, according to similarities with surface marker profiles of several known cell types. Human primary chondrosarcoma cells, articular chondrocytes, mesenchymal stem cells, fibroblasts, and a panel of tumor cell lines from chondrocytic or epithelial origin were clustered based on the expression profile of eleven surface markers. For clustering, eight hierarchical clustering algorithms, three distance metrics, as well as several approaches for data preprocessing, including multivariate outlier detection, logarithmic transformation, and z-score normalization, were systematically evaluated. By selecting clustering approaches shown to give reproducible results for cluster recovery of known cell types, primary conventional central chondrosacoma cells could be grouped in two main clusters with distinctive marker expression signatures: one group clustering together with mesenchymal stem cells (CD49b-high/CD10-low/CD221-high) and a second group clustering close to fibroblasts (CD49b-low/CD10-high/CD221-low). Hierarchical clustering also revealed substantial differences between primary conventional central chondrosarcoma cells and established chondrosarcoma cell lines, with the latter not only segregating apart from primary tumor cells and normal tissue cells, but clustering together with cell lines from epithelial lineage. Our study provides a foundation for the use of hierarchical clustering applied to flow cytometry data as a powerful tool to classify samples according to marker expression patterns, which could lead to uncover new cancer subtypes.

Pheochromocytoma in rats with multiple endocrine neoplasia (MENX) shares gene expression patterns with human pheochromocytoma

Pheochromocytomas are rare neoplasias of neural crest origin arising from chromaffin cells of the adrenal medulla and sympathetic ganglia (extra-adrenal pheochromocytoma). Pheochromocytoma that develop in rats homozygous for a loss-of-function mutation in p27Kip1 (MENX syndrome) show a clear progression from hyperplasia to tumor, offering the possibility to gain insight into tumor pathobiology. We compared the gene-expression signatures of both adrenomedullary hyperplasia and pheochromocytoma with normal rat adrenal medulla. Hyperplasia and tumor show very similar transcriptome profiles, indicating early determination of the tumorigenic signature. Overrepresentation of developmentally regulated neural genes was a feature of the rat lesions. Quantitative RT-PCR validated the up-regulation of 11 genes, including some involved in neural development: Cdkn2a, Cdkn2c, Neurod1, Gal, Bmp7, and Phox2a. Overexpression of these genes precedes histological changes in affected adrenal glands. Their presence at early stages of tumorigenesis indicates they are not acquired during progression and may be a result of the lack of functional p27Kip1. Adrenal and extra-adrenal pheochromocytoma development clearly follows diverged molecular pathways in MENX rats. To correlate these findings to human pheochromocytoma, we studied nine genes overexpressed in the rat lesions in 46 sporadic and familial human pheochromocytomas. The expression of GAL, DGKH, BMP7, PHOX2A, L1CAM, TCTE1, EBF3, SOX4, and HASH1 was up-regulated, although with different frequencies. Immunohistochemical staining detected high L1CAM expression selectively in 27 human pheochromocytomas but not in 140 nonchromaffin neuroendocrine tumors. These studies reveal clues to the molecular pathways involved in rat and human pheochromocytoma and identify previously unexplored biomarkers for clinical use.

Informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry (GCxGC-HRMS)

This paper describes informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography (GCxGC) and high-resolution mass spectrometry (HRMS). GCxGC-HRMS analysis produces large data sets that are rich with information, but highly complex. The size of the data and volume of information requires automated processing for comprehensive cross-sample analysis, but the complexity poses a challenge for developing robust methods. The approach developed here analyzes GCxGC-HRMS data from multiple samples to extract a feature template that comprehensively captures the pattern of peaks detected in the retention-times plane. Then, for each sample chromatogram, the template is geometrically transformed to align with the detected peak pattern and generate a set of feature measurements for cross-sample analyses such as sample classification and biomarker discovery. The approach avoids the intractable problem of comprehensive peak matching by using a few reliable peaks for alignment and peak-based retention-plane windows to define comprehensive features that can be reliably matched for cross-sample analysis. The informatics are demonstrated with a set of 18 samples from breast-cancer tumors, each from different individuals, six each for Grades 1-3. The features allow classification that matches grading by a cancer pathologist with 78% success in leave-one-out cross-validation experiments. The HRMS signatures of the features of interest can be examined for determining elemental compositions and identifying compounds.

The Spatial Signature of Biotic Interactions of a Clonal and a Non-clonal Palmetto in a Subtropical Plant Community

Spatial analyses of plant-distribution patterns can provide inferences about intra- and interspecific biotic interactions. Yet, such analyses are rare for clonal plants because effective tools (i.e., molecular markers) needed to map naturally occurring clonal individuals have only become available recently. Clonal plants are unique in that a single genotype has a potential to spatially place new individuals (i.e., ramets) in response to intra- and interspecific biotic interactions. Laboratory and greenhouse studies suggest that some clonal plants can avoid intra-genet, inter-genet, and inter-specific competition via rootplacement patterns. An intriguing and yet to be explored question is whether a spatial signature of such multi-level biotic interactions can be detected in natural plant communities. The facultatively clonal Serenoa repens and non-clonal Sabal etonia are ecologically similar and co-dominant palmettos that sympatrically occur in the Florida peninsula. We used amplified fragment length polymorphisms (AFLPs) to identify Serenoa genets and also to assign field-unidentifiable small individuals as Sabal seedlings, Serenoa seedlings, or Serenoa vegetative sprouts. Then, we conducted univariate and bivariate multi-distance spatial analyses to examine the spatial interactions of Serenoa (n=271) and Sabal (n=137) within a 20x20 m grid at three levels, intragenet, intergenet and interspecific. We found that spatial interactions were not random at all three levels of biotic interactions. Serenoa genets appear to spatially avoid self-competition as well as intergenet competition. Furthermore, Serenoa and Sabal were spatially negatively associated with each other. However, this negative association pattern was also evident in a spatial comparison between non-clonal Serenoa and Sabal, suggesting that Serenoa genets’ spatial avoidance of Sabal through placement of new ramets is not the explanation of the interspecific-level negative spatial pattern. Our results emphasize the importance of investigating spatial signatures of biotic as well as abiotic interactions at multiple levels in understanding spatial distribution patterns of clonal plants in natural plant communities.

The Extremely Red, Young L Dwarf PSO J318.5338-22.8603: a Free-Floating Planetary-Mass Analog to Directly Imaged Young Gas-Giant Planets

We have discovered using Pan-STARRS1 an extremely red late-L dwarf, which has (J - K)(MKO) = 2.78 and (J - K) (2MASS) = 2.84, making it the reddest known field dwarf and second only to 2MASS J1207-39b among substellar companions. Near-IR spectroscopy shows a spectral type of L7 +/- 1 and reveals a triangular H-band continuum and weak alkali (K I and Na I) lines, hallmarks of low surface gravity. Near-IR astrometry from the Hawaii Infrared Parallax Program gives a distance of 24.6 +/- 1.4 pc and indicates a much fainter J-band absolute magnitude than field L dwarfs. The position and kinematics of PSO J318.5-22 point to membership in the beta Pic moving group. Evolutionary models give a temperature of 1160(-40)(+30) K and a mass of 6.5(-1.0)(+1.3) M-Jup, making PSO J318.5-22 one of the lowest mass free-floating objects in the solar neighborhood. This object adds to the growing list of low-gravity field L dwarfs and is the first to be strongly deficient in methane relative to its estimated temperature. Comparing their spectra suggests that young L dwarfs with similar ages and temperatures can have different spectral signatures of youth. For the two objects with well constrained ages (PSO J318.5-22 and 2MASS J0355+11), we find their temperatures are approximate to 400 K cooler than field objects of similar spectral type but their luminosities are similar, i.e., these young L dwarfs are very red and unusually cool but not "underluminous." Altogether, PSO J318.5-22 is the first free-floating object with the colors, magnitudes, spectrum, luminosity, and mass that overlap the young dusty planets around HR 8799 and 2MASS J1207-39

Quantification of the carbonaceous matter origin in submicron marine aerosol by 13C and 14C isotope analysis

Dual carbon isotope anal. of marine aerosol samples has been performed for the first time demonstrating a potential in org. matter apportionment between three principal sources: marine, terrestrial (non-fossil) and fossil fuel due to unique isotopic signatures. The results presented here, utilizing combinations of dual carbon isotope anal., provides conclusive evidence of a dominant biogenic org. fraction to org. aerosol over biol. active oceans. In particular, the NE Atlantic, which is also subjected to notable anthropogenic influences via pollution transport processes, was found to contain 80 % org. aerosol matter of biogenic origin directly linked to plankton emissions. The remaining carbonaceous aerosol was of terrestrial origin. By contrast, for polluted air advected out from Europe into the NE Atlantic, the source apportionment is 30 % marine biogenic, 40 % fossil fuel, and 30 % continental non-fossil fuel. The dominant marine org. aerosol source in the atm. has significant implications for climate change feedback processes. [on SciFinder(R)]

Ion fractionation in young sea ice from Kongsfjorden, Svalbard

The fractionation of major sea-water ions, or deviation in their relative concentrations from Standard Mean Ocean Water ratios, has been frequently observed in sea ice. It is generally thought to be associated with precipitation of solid salts at certain eutectic temperatures. The variability found in bulk sea-ice samples indicates that the fractionation of ions depends on the often unknown thermal history of sea ice, which affects the structure of pore networks and fate of solid salts within them. Here we investigate the distribution of ions in Arctic sea ice that is a few weeks old with a reconstructible thermal history. We separate the centrifugable (interconnected) and entrapped (likely disconnected) contributions to the ice salinity and determine their ion fractionation signatures. The results indicate that differential diffusion of ions, rather than eutectic precipitation of cryohydrates, has led to significant ion fractionation. The finding emphasizes the role of coupled diffusive–convective salt transport through complex pore networks in shaping the biogeochemistry of sea ice.

Population genomic tests of models of adaptive radiation in Lake Victoria Region cichlid fish

Adaptive radiation is usually thought to be associated with speciation, but the evolution of intraspecific polymorphisms without speciation is also possible. The radiation of cichlid fish in Lake Victoria (LV) is perhaps the most impressive example of a recent rapid adaptive radiation, with 600+ very young species. Key questions about its origin remain poorly characterized, such as the importance of speciation versus polymorphism, whether species persist on evolutionary time scales, and if speciation happens more commonly in small isolated or in large connected populations. We used 320 individuals from 105 putative species from Lakes Victoria, Edward, Kivu, Albert, Nabugabo and Saka, in a radiation-wide amplified fragment length polymorphism (AFLP) genome scan to address some of these questions. We demonstrate pervasive signatures of speciation supporting the classical model of adaptive radiation associated with speciation. A positive relationship between the age of lakes and the average genomic differentiation of their species, and a significant fraction of molecular variance explained by above-species level taxonomy suggest the persistence of species on evolutionary time scales, with radiation through sequential speciation rather than a single starburst. Finally the large gene diversity retained from colonization to individual species in every radiation suggests large effective population sizes and makes speciation in small geographical isolates unlikely.

Observations of middle atmospheric H2O and O3 during the 2010 major sudden stratospheric warming by a network of microwave radiometers

In this study, we present middle atmospheric water vapor (H2O) and ozone (O3) measurements obtained by ground-based microwave radiometers at three European locations in Bern (47° N), Onsala (57° N) and Sodankylä (67° N) during Northern winter 2009/2010. In January 2010, a major sudden stratospheric warming (SSW) occurred in the Northern Hemisphere whose signatures are evident in the ground-based observations of H2O and O3. The observed anomalies in H2O and O3 are mostly explained by the relative location of the polar vortex with respect to the measurement locations. The SSW started on 26 January 2010 and was most pronounced by the end of January. The zonal mean temperature in the middle stratosphere (10 hPa) increased by approximately 25 Kelvin within a few days. The stratospheric vortex weakened during the SSW and shifted towards Europe. In the mesosphere, the vortex broke down, which lead to large scale mixing of polar and midlatitudinal air. After the warming, the polar vortex in the stratosphere split into two weaker vortices and in the mesosphere, a new, pole-centered vortex formed with maximum wind speed of 70 m s−1 at approximately 40° N. The shift of the stratospheric vortex towards Europe was observed in Bern as an increase in stratospheric H2O and a decrease in O3. The breakdown of the mesospheric vortex during the SSW was observed at Onsala and Sodankylä as a sudden increase in mesospheric H2O. The following large-scale descent inside the newly formed mesospheric vortex was well captured by the H2O observations in Sodankylä. In order to combine the H2O observations from the three different locations, we applied the trajectory mapping technique on our H2O observations to derive synoptic scale maps of the H2O distribution. Based on our observations and the 3-D wind field, this method allows determining the approximate development of the stratospheric and mesospheric polar vortex and demonstrates the potential of a network of ground-based instruments.

Natural tracer profiles across argillaceous formations

Argillaceous formations generally act as aquitards because of their low hydraulic conductivities. This property, together with the large retention capacity of clays for cationic contaminants, has brought argillaceous formations into focus as potential host rocks for the geological disposal of radioactive and other waste. In several countries, programmes are under way to characterise the detailed transport properties of such formations at depth. In this context, the interpretation of profiles of natural tracers in pore waters across the formations can give valuable information about the large-scale and long-term transport behaviour of these formations. Here, tracer-profile data, obtained by various methods of pore-water extraction for nine sites in central Europe, are compiled. Data at each site comprise some or all of the conservative tracers: anions (Cl(-), Br(-)), water isotopes (delta(18)O, delta(2)H) and noble gases (mainly He). Based on a careful evaluation of the palaeo-hydrogeological evolution at each site, model scenarios are derived for initial and boundary pore-water compositions and an attempt is made to numerically reproduce the observed tracer distributions in a consistent way for all tracers and sites, using transport parameters derived from laboratory or in situ tests. The comprehensive results from this project have been reported in Mazurek et al. (2009). Here the results for three sites are presented in detail, but the conclusions are based on model interpretations of the entire data set. In essentially all cases, the shapes of the profiles can be explained by diffusion acting as the dominant transport process over periods of several thousands to several millions of years and at the length scales of the profiles. Transport by advection has a negligible influence on the observed profiles at most sites, as can be shown by estimating the maximum advection velocities that still give acceptable fits of the model with the data. The advantages and disadvantages of different conservative tracers are also assessed. The anion Cl(-) is well suited as a natural tracer in aquitards, because its concentration varies considerably in environmental waters. It can easily be measured, although the uncertainty regarding the fraction of the pore space that is accessible to anions in clays remains an issue. The stable water isotopes are also well suited, but they are more difficult to measure and their values generally exhibit a smaller relative range of variation. Chlorine isotopes (delta(37)Cl) and He are more difficult to interpret because initial and boundary conditions cannot easily be constrained by independent evidence. It is also shown that the existence of perturbing events such as the activation of aquifers due to uplift and erosion, leading to relatively sharp changes of boundary conditions, can be considered as a pre-requisite to obtain well-interpretable tracer signatures. On the other hand, gradual changes of boundary conditions are more difficult to parameterise and so may preclude a clear interpretation.

Expression profiling of stem cell-related genes in neoadjuvant-treated gastric cancer: a NOTCH2, GSK3B and β-catenin gene signature predicts survival

Cancer stem cell (CSC) based gene expression signatures are associated with prognosis in various tumour types and CSCs are suggested to be particularly drug resistant. The aim of our study was first, to determine the prognostic significance of CSC-related gene expression in residual tumour cells of neoadjuvant-treated gastric cancer (GC) patients. Second, we wished to examine, whether expression alterations between pre- and post-therapeutic tumour samples exist, consistent with an enrichment of drug resistant tumour cells. The expression of 44 genes was analysed in 63 formalin-fixed, paraffin embedded tumour specimens with partial tumour regression (10-50% residual tumour) after neoadjuvant chemotherapy by quantitative real time PCR low-density arrays. A signature of combined GSK3B(high), β-catenin (CTNNB1)(high) and NOTCH2(low) expression was strongly correlated with better patient survival (p<0.001). A prognostic relevance of these genes was also found analysing publically available gene expression data. The expression of 9 genes was compared between pre-therapeutic biopsies and post-therapeutic resected specimens. A significant post-therapeutic increase in NOTCH2, LGR5 and POU5F1 expression was found in tumours with different tumour regression grades. No significant alterations were observed for GSK3B and CTNNB1. Immunohistochemical analysis demonstrated a chemotherapy-associated increase in the intensity of NOTCH2 staining, but not in the percentage of NOTCH2. Taken together, the GSK3B, CTNNB1 and NOTCH2 expression signature is a novel, promising prognostic parameter for GC. The results of the differential expression analysis indicate a prominent role for NOTCH2 and chemotherapy resistance in GC, which seems to be related to an effect of the drugs on NOTCH2 expression rather than to an enrichment of NOTCH2 expressing tumour cells.

Tumor classification of six common cancer types based on proteomic profiling by MALDI imaging

In clinical diagnostics, it is of outmost importance to correctly identify the source of a metastatic tumor, especially if no apparent primary tumor is present. Tissue-based proteomics might allow correct tumor classification. As a result, we performed MALDI imaging to generate proteomic signatures for different tumors. These signatures were used to classify common cancer types. At first, a cohort comprised of tissue samples from six adenocarcinoma entities located at different organ sites (esophagus, breast, colon, liver, stomach, thyroid gland, n = 171) was classified using two algorithms for a training and test set. For the test set, Support Vector Machine and Random Forest yielded overall accuracies of 82.74 and 81.18%, respectively. Then, colon cancer liver metastasis samples (n = 19) were introduced into the classification. The liver metastasis samples could be discriminated with high accuracy from primary tumors of colon cancer and hepatocellular carcinoma. Additionally, colon cancer liver metastasis samples could be successfully classified by using colon cancer primary tumor samples for the training of the classifier. These findings demonstrate that MALDI imaging-derived proteomic classifiers can discriminate between different tumor types at different organ sites and in the same site.