A new multimodal paradigm for biomarkers longitudinal monitoring: a clinical application to women steroid profiles in urine and blood.

Most current state-of-the-art strategies to generate individual adaptive reference ranges are designed to monitor one clinical parameter at a time. An innovative methodology is proposed for the simultaneous longitudinal monitoring of multiple biomarkers. The estimation of individual thresholds is performed by applying a Bayesian modeling strategy to a multivariate score integrating several biomarkers (compound concentration and/or ratio). This multimodal monitoring was applied to data from a clinical study involving 14 female volunteers with normal menstrual cycles receiving testosterone via transdermal route, as to test its ability to detect testosterone administration. The study samples consisted of urine and blood collected during 4 weeks of a control phase and 4 weeks with a daily testosterone gel application. Integrating multiple biomarkers improved the detection of testosterone gel administration with substantially higher sensitivity compared with the distinct follow-up of each biomarker, when applied to selected urine and serum steroid biomarkers, as well as the combination of both. Among the 175 known positive samples, 38% were identified by the multimodal approach using urine biomarkers, 79% using serum biomarkers and 83% by combining biomarkers from both biological matrices, whereas 10%, 67% and 64% were respectively detected using standard unimodal monitoring. The detection of abnormal patterns can be improved using multimodal approaches. The combination of urine and serum biomarkers reduced the overall number of false-negatives, thus evidencing promising complementarity between urine and blood sampling for doping control, as highlighted in the case of the use of transdermal testosterone preparations. The generation in a multimodal setting of adaptive and personalized reference ranges opens up new opportunities in clinical and anti-doping profiling. The integration of multiple parameters in a longitudinal monitoring is expected to provide a more complete evaluation of individual profiles generating actionable intelligence to further guide sample collection, analysis protocols and decision-making in clinics and anti-doping

Coupling Impedance of the CERN SPS beam position monitors

A detailed knowledge of the beam coupling impedance of the CERN Super Proton Synchrotron (SPS) is required in order to operate this machine with a higher intensity for the foreseen Large Hadron Collider (LHC) luminosity upgrade. A large number of Beam Position Monitors (BPMs) is currently installed in the SPS, and this is why their contribution to the SPS impedance has to be assessed. This paper focuses on electromagnetic (EM) simulations and bench measurements of the longitudinal and transverse impedance generated by the horizontal and vertical BPMs installed in the SPS machine

High-resolution mass spectrometry as an alternative detection method to tandem mass spectrometry for the analysis of endogenous steroids in serum.

Recently, steroid hormones quantification in blood showed a promising ability to detect testosterone doping and interesting complementarities with the urinary module of the Athlete Biological Passport (ABP). In this work, an ultra-high pressure liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) method was developed for the quantification of eleven endogenous steroids in serum. The performance of the full scan and targeted SIM acquisition modes was evaluated and compared to the performance of tandem mass spectrometry (MS/MS). Passing-Bablok regressions and Bland-Altman plots were assessed for each analyte of interest, and concentration values measured by HRMS showed high correlation with the ones obtained by MS/MS for all target hormones, with low absolute differences in the majority of cases. A slight decrease in terms of sensitivity was observed with HRMS in both acquisition modes, but performing an analysis of variance multiblock orthogonal partial least squares (AMOPLS) on the dataset obtained with all three methods revealed that only 0.8% of the total variance was related to instrumentation and acquisition methods. Moreover, the evaluation of the testosterone administration effect over time highlighted testosterone itself and dihydrotestosterone as the most promising biomarkers of exogenous testosterone administration. This conclusion suggests that HRMS could provide suitable performance for blood steroid analysis in the anti-doping field

Recent advances and remaining challenges in thin-film silicon photovoltaic technology

This contribution reviews some of the latest achievements and challenges in thin-film silicon photovoltaic (PV) technology based on amorphous and nanocrystalline silicon and their alloys. We address material and device developments, including (i) improved plasma deposition processes to achieve high-quality dense absorber materials; (ii) absorber layers based on silicon tetrafluoride, which lead to enhanced absorption in the near-infrared and yield outstanding short-circuit current densities; (iii) dedicated optimization of the interfaces and device architecture, as well as (iv) enhanced light harvesting by means of multi-scale textured substrates and reduced parasitic absorption in the non-active layers. This paper will describe how, by combining all of these advances along with precise control of plasmas over large areas, key results have been achieved in recent years, at both the cell and large-area module level, with stabilized efficiencies of over 13 and 12%, respectively

Gene clusters reflecting macrodomain structure respond to nucleoid perturbations

Focusing on the DNA-bridging nucleoid proteins Fis and H-NS, and integrating several independent experimental and bioinformatic data sources, we investigate the links between chromosomal spatial organization and global transcriptional regulation. By means of a novel multi-scale spatial aggregation analysis, we uncover the existence of contiguous clusters of nucleoid-perturbation sensitive genes along the genome, whose expression is affected by a combination of topological DNA state and nucleoid-shaping protein occupancy. The clusters correlate well with the macrodomain structure of the genome. The most significant of them lay symmetrically at the edges of the ter macrodomain and involve all of the flagellar and chemotaxis machinery, in addition to key regulators of biofilm formation, suggesting that the regulation of the physical state of the chromosome by the nucleoid proteins plays an important role in coordinating the transcriptional response leading to the switch between a motile and a biofilm lifestyle.Comment: Article: first 24 pages, 3 figures Supplementary methods: 1 page, 1 figure Supplementary results: 14 pages, 11 figure

ZnO Transparent conductive oxide for thin film silicon solar cells

There is general agreement that the future production of electric energy has to be renewable and sustainable in the long term. Photovoltaic (PV) is booming with more than 7GW produced in 2008 and will therefore play an important role in the future electricity supply mix. Currently, crystalline silicon (c-Si) dominates the market with a share of about 90%. Reducing the cost per watt peak and energy pay back time of PV was the major concern of the last decade and remains the main challenge today. For that, thin film silicon solar cells has a strong potential because it allies the strength of c-Si (i.e. durability, abundancy, non toxicity) together with reduced material usage, lower temperature processes and monolithic interconnection. One of the technological key points is the transparent conductive oxide (TCO) used for front contact, barrier layer or intermediate reflector. In this paper, we report on the versatility of ZnO grown by low pressure chemical vapor deposition (ZnO LP-CVD) and its application in thin film silicon solar cells. In particular, we focus on the transparency, the morphology of the textured surface and its effects on the light in-coupling for micromorph tandem cells in both the substrate (n-i-p) and superstrate (p-i-n) configurations. The stabilized efficiencies achieved in Neuchâtel are 11.2% and 9.8% for p-i-n (without ARC) and n-i-p (plastic substrate), respectively

DynaStI: A Dynamic Retention Time Database for Steroidomics.

: Steroidomics studies face the challenge of separating analytical compounds with very similar structures (i.e., isomers). Liquid chromatography (LC) is commonly used to this end, but the shared core structure of this family of compounds compromises effective separations among the numerous chemical analytes with comparable physico-chemical properties. Careful tuning of the mobile phase gradient and an appropriate choice of the stationary phase can be used to overcome this problem, in turn modifying the retention times in different ways for each compound. In the usual workflow, this approach is suboptimal for the annotation of features based on retention times since it requires characterizing a library of known compounds for every fine-tuned configuration. We introduce a software solution, DynaStI, that is capable of annotating liquid chromatography-mass spectrometry (LC-MS) features by dynamically generating the retention times from a database containing intrinsic properties of a library of metabolites. DynaStI uses the well-established linear solvent strength (LSS) model for reversed-phase LC. Given a list of LC-MS features and some characteristics of the LC setup, this software computes the corresponding retention times for the internal database and then annotates the features using the exact masses with predicted retention times at the working conditions. DynaStI (https://dynasti.vital-it.ch) is able to automatically calibrate its predictions to compensate for deviations in the input parameters. The database also includes identification and structural information for each annotation, such as IUPAC name, CAS number, SMILES string, metabolic pathways, and links to external metabolomic or lipidomic databases

Breast cancer resistance protein (BCRP/ABCG2): New inhibitors and QSAR studies by a 3D linear solvation energy approach

A series of compounds derived from naturally occurring flavonoids and synthetic analogs have been evaluated on cell lines overexpressing the wild-type breast cancer resistance protein (BCRP/ABCG2) half-transporter. Human ABCG2-transfected cells were used for screening their inhibitory activity. Five new natural compounds obtained from Morus mesozygia Stapf and one synthetic chromone, comprising a flavonoidic scaffold, were also evaluated. Based on the results obtained with a total of 34 compounds, a 3D linear solvation energy QSAR was investigated by VolSurf descriptors of molecular-interaction fields (MIFs) related to hydrophobic-interaction forces, polarisability and hydrogen-bonding capacity. Accuracy of the constructed 3D-QSAR model was attested by a correlation coefficient r2 of 0.77. Shape parameters and hydrophobicity were revealed to be major physicochemical parameters responsible for the inhibition activity of flavonoid derivatives and synthetic analogs towards ABCG2, whereas hydrogen-bond donor capacity appeared highly unfavorable