A new strategy for faster urinary biomarkers identification by Nano-LC-MALDI-TOF/TOF mass spectrometry

<p>Abstract</p> <p>Background</p> <p>LC-MALDI-TOF/TOF analysis is a potent tool in biomarkers discovery characterized by its high sensitivity and high throughput capacity. However, methods based on MALDI-TOF/TOF for biomarkers discovery still need optimization, in particular to reduce analysis time and to evaluate their reproducibility for peak intensities measurement. The aims of this methodological study were: (i) to optimize and critically evaluate each step of urine biomarker discovery method based on Nano-LC coupled off-line to MALDI-TOF/TOF, taking full advantage of the dual decoupling between Nano-LC, MS and MS/MS to reduce the overall analysis time; (ii) to evaluate the quantitative performance and reproducibility of nano-LC-MALDI analysis in biomarker discovery; and (iii) to evaluate the robustness of biomarkers selection.</p> <p>Results</p> <p>A pool of urine sample spiked at increasing concentrations with a mixture of standard peptides was used as a specimen for biological samples with or without biomarkers. Extraction and nano-LC-MS variabilities were estimated by analyzing in triplicates and hexaplicates, respectively. The stability of chromatographic fractions immobilised with MALDI matrix on MALDI plates was evaluated by successive MS acquisitions after different storage times at different temperatures.</p> <p>Low coefficient of variation (CV%: 10–22%) and high correlation (R²> 0.96) values were obtained for the quantification of the spiked peptides, allowing quantification of these peptides in the low fentomole range, correct group discrimination and selection of "specific" markers using principal component analysis. Excellent peptide integrity and stable signal intensity were found when MALDI plates were stored for periods of up to 2 months at +4°C. This allowed storage of MALDI plates between LC separation and MS acquisition (first decoupling), and between MS and MSMS acquisitions while the selection of inter-group discriminative ions is done (second decoupling). Finally the recording of MSMS spectra to obtain structural information was focused only on discriminative ions in order to minimize analysis time.</p> <p>Conclusion</p> <p>Contrary to other classical approaches with direct online coupling of chromatographic separation and on the flight MS and/or MSMS data acquisition for all detected analytes, our dual decoupling strategy allowed us to focus on the most discriminative analytes, giving us more time to acquire more replicates of the same urine samples thus increasing detection sensitivity and mass precision.</p

Results of the EUROTeV Beam-Beam Simulation (BBSIM) Task

This paper is the deliverable of the EUROTeV Beam-Beam Simulation (BBSIM) task and gives an overview of the published results

The Intrinsic Fundamental Group of a Linear Category

We provide an intrinsic definition of the fundamental group of a linear category over a ring as the automorphism group of the fibre functor on Galois coverings. If the universal covering exists, we prove that this group is isomorphic to the Galois group of the universal covering. The grading deduced from a Galois covering enables us to describe the canonical monomorphism from its automorphism group to the first Hochschild-Mitchell cohomology vector space.Comment: Final version, to appear in Algebras and Representation Theor

Medicosocial outcome after admission in post-intensive care unit at PRM St-Hélier, Rennes

IntroductionPost-Intensive Care Units (PICU) are PRM structures aiming to start the appropriated rehabilitative care as early as possible even though persistent complex medical issues.ObjectiveTo assess medicosocial outcomes of patients away from their admission in PICU.MethodsA retrospective descriptive study that included 81 consecutive patients (mean age 51 years) admitted from 2008 to 2012 in the PICU of Pôle St-Helier Rennes based on called semi-structured interviews between March 2014 and March 2015. Exhaustive data (only 4 lost, 5%) by the patient himself and/or a member of family on autonomy, place of life, structures since the release and reintegration, of patients for 85% of them brain damaged.ResultsThere is 29% (21/77) of death (post-exit life: 1,6 years±1.18). Eighty percent live at home (46/56) of which only 5 without family environment, 10% (5/56) in medicosocial structures (foster or nursing homes…), 10% in hospital (hospital at home, persistent vegetative units…). Fourteen percent (8/56) are completely autonomous and work, all with adaptations. Twenty-three percent (13/56) had a significant dependence for activities of daily life and instrumental ones. Forty percent (22/56) have no hobby. Use of different downstream structures, long-term readaptative monitoring, legal and families’ feelings were also analyzed.Discussion and ConclusionMedical and social outcome of patients in the aftermath of a stay in PICU is disparate, depending on the pathology involved, but also the pre-social situation that seems to be the main predictor of returning home. Most patients have regained a relatively large autonomy for the daily life activities but are embarrassed to complex instrumental activities impeding social inclusion. These results are consistent with those of the literature on head trauma patients but no other study has focused for the moment on the specific population of patients admitted to the PICU. We see the value of such early rehabilitative care units with a real impact on the subsequent independence and opportunities back home

A nonextensive approach to Bose-Einstein condensation of trapped interacting boson gas

In the Bose-Einstein condensation of interacting atoms or molecules such as 87Rb, 23Na and 7Li, the theoretical understanding of the transition temperature is not always obvious due to the interactions or zero point energy which cannot be exactly taken into account. The S-wave collision model fails sometimes to account for the condensation temperatures. In this work, we look at the problem within the nonextensive statistics which is considered as a possible theory describing interacting systems. The generalized energy Uq and the particle number Nq of boson gas are given in terms of the nonextensive parameter q. q>1 (q<1) implies repulsive (attractive) interaction with respect to the perfect gas. The generalized condensation temperature Tcq is derived versus Tc given by the perfect gas theory. Thanks to the observed condensation temperatures, we find q ~ 0.1 for 87Rb atomic gas, q ~ 0.95 for 7Li and q ~ 0.62 for 23Na. It is concluded that the effective interactions are essentially attractive for the three considered atoms, which is consistent with the observed temperatures higher than those predicted by the conventional theory

Mining regulatory 5′UTRs from cDNA deep sequencing datasets

Regulatory 5′ untranslated regions (r5′UTRs) of mRNAs such as riboswitches modulate the expression of genes involved in varied biological processes in both bacteria and eukaryotes. New high-throughput sequencing technologies could provide powerful tools for discovery of novel r5′UTRs, but the size and complexity of the datasets generated by these technologies makes it difficult to differentiate r5′UTRs from the multitude of other types of RNAs detected. Here, we developed and implemented a bioinformatic approach to identify putative r5′UTRs from within large datasets of RNAs recently identified by pyrosequencing of the Vibrio cholerae small transcriptome. This screen yielded only ∼1% of all non-overlapping RNAs along with 75% of previously annotated r5′UTRs and 69 candidate V. cholerae r5′UTRs. These candidates include several putative functional homologues of diverse r5′UTRs characterized in other species as well as numerous candidates upstream of genes involved in pathways not known to be regulated by r5′UTRs, such as fatty acid oxidation and peptidoglycan catabolism. Two of these novel r5′UTRs were experimentally validated using a GFP reporter-based approach. Our findings suggest that the number and diversity of pathways regulated by r5′UTRs has been underestimated and that deep sequencing-based transcriptomics will be extremely valuable in the search for novel r5′UTRs

Saliency Benchmarking Made Easy: Separating Models, Maps and Metrics

Dozens of new models on fixation prediction are published every year and compared on open benchmarks such as MIT300 and LSUN. However, progress in the field can be difficult to judge because models are compared using a variety of inconsistent metrics. Here we show that no single saliency map can perform well under all metrics. Instead, we propose a principled approach to solve the benchmarking problem by separating the notions of saliency models, maps and metrics. Inspired by Bayesian decision theory, we define a saliency model to be a probabilistic model of fixation density prediction and a saliency map to be a metric-specific prediction derived from the model density which maximizes the expected performance on that metric given the model density. We derive these optimal saliency maps for the most commonly used saliency metrics (AUC, sAUC, NSS, CC, SIM, KL-Div) and show that they can be computed analytically or approximated with high precision. We show that this leads to consistent rankings in all metrics and avoids the penalties of using one saliency map for all metrics. Our method allows researchers to have their model compete on many different metrics with state-of-the-art in those metrics: "good" models will perform well in all metrics.Comment: published at ECCV 201