Metabolomics reveals biomarkers in human urine and plasma to predict cytochrome P450 2D6 (CYP2D6) activity.

Individualized assessment of cytochrome P450 2D6 (CYP2D6) activity is usually performed through phenotyping following administration of a probe drug to measure the enzyme's activity. To avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe drug, the development of non-burdensome tools for real-time phenotyping of CYP2D6 could significantly contribute to precision medicine. This study focuses on the identification of markers of the CYP2D6 enzyme in human biofluids using an LC-high-resolution mass spectrometry-based metabolomic approach. Plasma and urine samples from healthy volunteers were analysed before and after intake of a daily dose of paroxetine 20 mg over 7 days. CYP2D6 genotyping and phenotyping, using single oral dose of dextromethorphan 5 mg, were also performed in all participants. We report four metabolites of solanidine and two unknown compounds as possible novel CYP2D6 markers. Mean relative intensities of these features were significantly reduced during the inhibition session compared with the control session (n = 37). Semi-quantitative analysis showed that the largest decrease (-85%) was observed for the ion m/z 432.3108 normalized to solanidine (m/z 398.3417). Mean relative intensities of these ions were significantly higher in the CYP2D6 normal-ultrarapid metabolizer group (n = 37) compared with the poor metabolizer group (n = 6). Solanidine intensity was more than 15 times higher in CYP2D6-deficient individuals compared with other volunteers. The applied untargeted metabolomic strategy identified potential novel markers capable of semi-quantitatively predicting CYP2D6 activity, a promising discovery for personalized medicine

The Density of States in High-Tc Superconductors Vortices

We calculated the electronic structure of a vortex in a pseudogapped superconductor within a model featuring strong correlations. With increasing strength of the correlations, the BCS core states are suppressed and the spectra in and outside the core become similar. If the correlations are short-range, we find new core states in agreement with the observations in YBaCuO and BiSrCaCuO. Our results point to a common phenomenology for these two systems and indicate that normal-state correlations survive below Tc without taking part in the overall phase coherence.Comment: REVTeX 4, 5 pages, 2 EPS figures. Some changes to the text; new figures; references update

Ambipolar gate effect and low temperature magnetoresistance of ultrathin La0.8Ca0.2MnO3 Films

Ultrathin La0.8Ca0.2MnO3 films have been measured in a field-effect geometry. The electric field due to the gate produces a large ambipolar decrease in resistance at low temperatures. This is attributed to the development of a pseudogap in the density of states and the couple of localized charge to strain. The gate effect and mangetoresistance are interpreted in a consistent framework. The implications for the low temperature behavior of a manganite film in the two dimensional limit are discussed.Comment: 4 pages, 3 figure

Geometric K-Homology of Flat D-Branes

We use the Baum-Douglas construction of K-homology to explicitly describe various aspects of D-branes in Type II superstring theory in the absence of background supergravity form fields. We rigorously derive various stability criteria for states of D-branes and show how standard bound state constructions are naturally realized directly in terms of topological K-cycles. We formulate the mechanism of flux stabilization in terms of the K-homology of non-trivial fibre bundles. Along the way we derive a number of new mathematical results in topological K-homology of independent interest.Comment: 45 pages; v2: References added; v3: Some substantial revision and corrections, main results unchanged but presentation improved, references added; to be published in Communications in Mathematical Physic

Measurement of Through-Going Particle Momentum By Means Of Multiple Scattering With The ICARUS T600 TPC

The ICARUS collaboration has demonstrated, following the operation of a 600 ton (T600) detector at shallow depth, that the technique based on liquid Argon TPCs is now mature. The study of rare events, not contemplated in the Standard Model, can greatly benefit from the use of this kind of detectors. In particular, a deeper understanding of atmospheric neutrino properties will be obtained thanks to the unprecedented quality of the data ICARUS provides. However if we concentrate on the T600 performance, most of the $\nu_\mu$ charged current sample will be partially contained, due to the reduced dimensions of the detector. In this article, we address the problem of how well we can determine the kinematics of events having partially contained tracks. The analysis of a large sample of atmospheric muons collected during the T600 test run demonstrate that, in case the recorded track is at least one meter long, the muon momentum can be reconstructed by an algorithm that measures the Multiple Coulomb Scattering along the particle's path. Moreover, we show that momentum resolution can be improved by a factor two using an algorithm based on the Kalman Filtering technique

The life cycle impact for platinum group metals and lithium to 2070 via surplus cost potential

© 2017 The Author(s)Purpose: A surplus cost potential (SCP) indicator has been developed as a measure of resource scarcity in the life cycle impact assessment (LCIA) context. To date, quality SCP estimates for other minerals than fossils are either not yet available or suffer methodological and data limitations. This paper overcomes these limitations and demonstrate how SCP estimates for metals can be calculated without the utilisation of ore grade function and by collecting primary economic and geological data. Methods: Data were collected in line with the geographical distribution, mine type, deposit type and production volumes and total production costs in order to construct cost-cumulative availability curves for platinum group metals (PGMs) and lithium. These curves capture the total amount of known mineral resources that can be recovered profitably at various prices from different types of mineral deposits under current conditions (this is, current technology, prevailing labour and other input prices). They served as a basis for modelling the marginal cost increase, a necessary parameter for estimating the SCP indicator. Surplus costs were calculated for different scenario projections for future mineral production considering future market dynamics, recyclability rates, demand-side technological developments and economic growth and by applying declining social discount rate. Results and discussion: Surplus costs were calculated for three mineral production scenarios, ranging from (US$2014/kg) 6545–8354 for platinum, 3583–4573 for palladium, 8281–10,569 for rhodium, 513–655 for ruthenium, 3201–4086 for iridium and 1.70–5.80 for lithium. Compared with the current production costs, the results indicate that problematic price increases of lithium are unlikely if the latest technological trends in the automotive sector will continue up to 2070. Surplus costs for PGMs are approximately one-third of the current production costs in all scenarios; hence, a threat of their price increases by 2070 will largely depend on the discovery of new deposits and the ability of new technologies to push these costs down over time. This also applies to lithium if the increasing electrification of road transport will continue up to 2070. Conclusions: This study provides useful insight into the availability of PGMs and lithium up to 2070. It proves that if time and resources permit, reliable surplus cost estimates can be calculated, at least in the short-run, based on the construction of one’s own curves with the level of quality comparable to expert-driven consulting services. Modelling and incorporating unknown deposits and potential future mineral production costs into these curves is the subject of future work

Measurement of the muon decay spectrum with the ICARUS liquid Argon TPC

Examples are given which prove the ICARUS detector quality through relevant physics measurements. We study the muon decay energy spectrum from a sample of stopping muon events acquired during the test run of the ICARUS T600 detector. This detector allows the spatial reconstruction of the events with fine granularity, hence, the precise measurement of the range and dE/dx of the muon with high sampling rate. This information is used to compute the calibration factors needed for the full calorimetric reconstruction of the events. The Michel rho parameter is then measured by comparison of the experimental and Monte Carlo simulated muon decay spectra, obtaining rho = 0.72 +/- 0.06(stat.) +/- 0.08(syst.). The energy resolution for electrons below ~50 MeV is finally extracted from the simulated sample, obtaining (Emeas-Emc)/Emc = 11%/sqrt(E[MeV]) + 2%.Comment: 16 pages, 8 figures, LaTex, A4. Some text and 1 figure added. Final version as accepted for publication in The European Physical Journal

Hidden heterochromatin: Characterization in the Rodentia species Cricetus cricetus, Peromyscus eremicus (Cricetidae) and Praomys tullbergi (Muridae)

The use of in situ restriction endonuclease (RE) (which cleaves DNA at specific sequences) digestion has proven to be a useful technique in improving the dissection of constitutive heterochromatin (CH), and in the understanding of the CH evolution in different genomes. In the present work we describe in detail the CH of the three Rodentia species, Cricetus cricetus, Peromyscus eremicus (family Cricetidae) and Praomys tullbergi (family Muridae) using a panel of seven REs followed by C-banding. Comparison of the amount, distribution and molecular nature of C-positive heterochromatin revealed molecular heterogeneity in the heterochromatin of the three species. The large number of subclasses of CH identified in Praomys tullbergi chromosomes indicated that the karyotype of this species is the more derived when compared with the other two genomes analyzed, probably originated by a great number of complex chromosomal rearrangements. The high level of sequence heterogeneity identified in the CH of the three genomes suggests the coexistence of different satellite DNA families, or variants of these families in these genomes

Spatial Resolution Attainable with Cathode Strip Chambers at the Trigger Level

A simple network of comparators applied to the strip signals of a cathode strip chamber allows quick hit localization to within a halfstrip width, or +/- a quarter-strip. A six-plane chamber with 6.4 mm wide strips was tested in a high-energy muon beam. The chamber was placed behind a 30 cm thick iron block. We show that patterns of hits localized to within a halfstrip allowed us to identify 300 GeV/c muon tracks with 99% probability and 0.7 mm spatial resolution in the presence of muon bremsstrahlung radiation. This technique of finding muon tracks will be used in the cathode strip chambers of the CMS Endcap Muon System