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.

Search for Quantum Black Hole Production in High-Invariant-Mass Lepton plus Jet Final States Using pp Collisions at root s=8 TeV and the ATLAS Detector

This Letter presents a search for quantum black-hole production using 20.3 fb(-1) of data collected with the ATLAS detector in pp collisions at the LHC at root s = 8 TeV. The quantum black holes are assumed to decay into a final state characterized by a lepton (electron or muon) and a jet. In either channel, no event with a lepton-jet invariant mass of 3.5 TeV or more is observed, consistent with the expected background. Limits are set on the product of cross sections and branching fractions for the lepton + jet final states of quantum black holes produced in a search region for invariant masses above 1 TeV. The combined 95% confidence level upper limit on this product for quantum black holes with threshold mass above 3.5 TeV is 0.18 fb. This limit constrains the threshold quantum black-hole mass to be above 5.3 TeV in the model considered.

Up-regulation of somatostatin receptor density on rat CA20948 tumors escaped from low dose [(177)Lu-DOTA(0),Tyr(3)]octreotate therapy

AIM: Peptide receptor radionuclide therapy using the somatostatin analogue [(177)Lu-DOTA(0),Tyr(3)]octreotate is a convincing treatment modality for metastasized neuroendocrine tumors. Therapeutic doses are administered in 4 cycles with 6-10 week intervals. A high somatostatin receptor density on tumor cells is a prerequisite at every administration to enable effective therapy. In this study, the density of the somatostatin receptor subtype 2 (sst2) was investigated in the rat CA20948 pancreatic tumor model after low dose [(177)Lu-DOTA(0), Tyr(3)]octreotate administration resulting in approximately 20 Gy tumor radiation absorbed dose, whereas 60 Gy is needed to induce complete tumor regression in these and the majority of tumors. METHODS: Sixteen days after inoculation of the CA20948 tumor, male Lewis rats were injected with 185 MBq [(177)Lu-DOTA(0),Tyr(3)]octreotate to initiate a decline in tumor size. Approximately 40 days after injection, tumors re-grew progressively after initial response. Quantification of sst2 expression was performed using in vitro autoradiography on frozen sections of three groups: control (not-treated) tumors, tumors in regression and tumors in re-growth. Histology and proliferation were determined using HE- and anti-Ki-67-staining. RESULTS: The sst2 expression on CA20948 tumor cells decreased significantly after therapy to 5% of control level. However, tumors escaping from therapy showed an up-regulated sst2 level of 2-5 times higher sst2 density compared to control tumors. CONCLUSION: After a suboptimal therapeutic dose of [(177)Lu-DOTA(0),Tyr(3)]octreotate, escape of tumors is likely to occur. Since these cells show an up-regulated sst2 receptor density, a next therapeutic administration of radiolabelled sst2 analogue can be expected to be highly effective.

The PLATO 2.0 mission

PLATO 2.0 has recently been selected for ESA’s M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s candence) providing a wide field-of-view (2232 deg 2) and a large photometric magnitude range (4–16 mag). It focusses on bright (4–11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4–10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2–3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e.g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmosphere. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA’s Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science.

Effects of divergent selection for growth on egg quality traits in Japanese quail

The experiment was designed to investigate the impact of selection for increased body mass on external and internal egg quality traits of Japanese quail. Three hundred and sixty Japanese quail, divergently selected over three generations for different body mass at 4 weeks of age, were used. Quail were homogeneously divided into three groups each consisting of 120 birds: high body mass (HBM), low body mass (LBM) and Control. ANOVA was used to detect the effect of selection on egg quality. In addition, correlation between external and internal egg quality traits was measured. Our results revealed thatHBMquail laid heavier eggs (P = 0.03 compared with LBM but not significantly different with Control quail) with a higher external (shell thickness, shell weight, eggshell ratio and eggshell density, P = 0.0001) and internal egg quality score (albumen weight, P = 0.003; albumen ratio, P = 0.01; albumen height, yolk height, yolk index and Haugh unit, P = 0.0001) when compared with both the Control and LBM. The egg surface area and yolk diameter were significantly higher in HBM when compared with the LBM but not with the Control line. Egg weight was positively correlated with albumen weight (r = 0.54, P = 0.0001), albumen ratio (r = 0.14, P = 0.05), yolk height (r = 0.27, P = 0.0001), yolk weight (r = 0.23, P = 0.002), yolk diameter (r = 0.14, P = 0.05) and yolk index (r = 0.21, P = 0.005) but was negatively correlated with yolk ratio (r = –0.16, P = 0.03). Our results indicate that selection for higher body mass might result in heavier eggs and superior egg quality.