A new clinically applicable immune-metabolic signature (IMMETCOLS) reveals metabolic singularities in consensus molecular subtypes (CMS) in colorectal cancer

Background: In the last years, a great effort has been made to unify different independent colorectal cancer (CRC) molecular classification systems into four consensus molecular subtypes (CMS). The four subtypes are found to be associated with distinct microenvironmental features and clinical outcome, although metabolic singularities are not well established. Metabolic dysregulation has been reported as a hallmark of CMS3, but metabolic heterogeneity among other subtypes has not been investigated. Here, taking into account the increasing evidence on the importance, for determining response to therapies, of the metabolic crosstalk between cancer cells, tumor microenvironment and immune cells, we investigated the metabolic singularities in the four CMS using a genetic immune-metabolic signature (IMMETCOLS). Conclusions: IMMETCOLS signature refines CMS prognosis in CRC patients and potentially allows specific metabolic interventions in CMS subtypes

A conceptual exoskeleton shoulder design for the assistance of upper limb movement

© Springer International Publishing AG, part of Springer Nature 2018. There is an increased interest on wearable technologies for rehabilitation and human augmentation. Systems focusing on the upper limbs are attempting to replicate the musculoskeletal structures found in humans, reproducing existing behaviors and capabilities. The current work is expanding on existing systems with a novel design that ensures the maximum range of motion while at the same time allowing for lockable features ensuring higher manipulation payloads at minimum energy and fatigue costs. An analysis of the biomechanics of the shoulder is being done and a detailed system design for structural as well actuation elements of a parallel mechanism is given. The benefits for the use are discussed of reduced weight, maximum range of motion at minimum energy cost

Non-deterministic Boolean Proof Nets

16 pagesInternational audienceWe introduce Non-deterministic Boolean proof nets to study the correspondence with Boolean circuits, a parallel model of computation. We extend the cut elimination of Non-deterministic Multiplicative Linear logic to a parallel procedure in proof nets. With the restriction of proof nets to Boolean types, we prove that the cut-elimination procedure corresponds to Non-deterministic Boolean circuit evaluation and reciprocally. We obtain implicit characterization of the complexity classes NP and NC (the efficiently parallelizable functions)

HARD PHOTON PRODUCTION IN NUCLEUS-NUCLEUS COLLISIONS AT 30 MeV/u AND 44 MeV/u

Doubly differential cross-sections for Bremsstrahlung production have been measured in the reactions 40Ar + 197Au at 30 MeV/u and 86Kr +12C, AgNat and 197Au at 44 MeV/u. A qualitative analysis of the characteristics of the γ-ray emission suggests strongly that the initial proton-neutron collisions are the main source of nuclear Bremsstrahlung

Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination

Axon–glial interactions are critical for the induction of myelination and the domain organization of myelinated fibers. Although molecular complexes that mediate these interactions in the nodal region are known, their counterparts along the internode are poorly defined. We report that neurons and Schwann cells express distinct sets of nectin-like (Necl) proteins: axons highly express Necl-1 and -2, whereas Schwann cells express Necl-4 and lower amounts of Necl-2. These proteins are strikingly localized to the internode, where Necl-1 and -2 on the axon are directly apposed by Necl-4 on the Schwann cell; all three proteins are also enriched at Schmidt-Lanterman incisures. Binding experiments demonstrate that the Necl proteins preferentially mediate heterophilic rather than homophilic interactions. In particular, Necl-1 on axons binds specifically to Necl-4 on Schwann cells. Knockdown of Necl-4 by short hairpin RNA inhibits Schwann cell differentiation and subsequent myelination in cocultures. These results demonstrate a key role for Necl-4 in initiating peripheral nervous system myelination and implicate the Necl proteins as mediators of axo–glial interactions along the internode

Innovation et gouvernance territoriale : une analyse par les dispositifs

International audienceCette communication vise à présenter les outils méthodologiques d'analyse/évaluation de la gouvernance territoriale élaborés dans le cadre du projet de recherche PSDR Gouv.Innov sur les innovations organisationnelles relatives à la gouvernance territoriale. Il s'agit d'étudier les transformations introduites par les politiques de développement durable au niveau des dispositifs de gouvernance territoriale visant à favoriser une gestion intégrée des espaces ruraux. Dans un contexte de recomposition de l'action publique où les procédures d'aménagement sont plutôt normées par des représentations urbaines, l'accent est mis sur la question des modalités de représentation des activités rurales, pour lesquelles nous faisons l'hypothèse qu'elles sont sous représentées. Les premiers résultats méthodologiques permettent, dans une première partie, de proposer une définition générique et pragmatique de la gouvernance territoriale et de préciser la notion de dispositifs de gouvernance comme objet d'observation. A partir de cette définition une grille d'analyse permettant d'appréhender l'ensemble des dimensions en jeu dans les processus de gouvernance territoriale est élaborée. Dans la deuxième partie nous explorons l'intérêt de la notion de dispositif pour observer les processus de gouvernance et proposons une grille de collecte et de structuration des informations pour constituer des chroniques des dispositifs étudiés. / This paper seeks to present the methodological tools used in the analysis/evaluation of territorial governance developed during research undertaken within the framework of the PSDR Gouv-Innov project on organisational innovations with respect to territorial governance. It involves the study of the changes resulting from the emergence of sustainable development policies in territorial governance systems aiming to implement the integrated management of rural areas. In a context of changes in the way in which public action is implemented (for instance, public-private partnerships), where development procedures are usually standardised by urban representations, the emphasis is placed on the issue of the representation of rural activities, the hypothesis being that they are under-represented. The initial methodological results lead, in the first instance, to a proposition for a generic and pragmatic definition of territorial governance and a clarification of the notion of governance systems as objects of observation. This definition can be used as the basis of a framework to address all the analytical dimensions of the territorial governance process. In the second part, the authors explore the idea of system in order to observe governance processes and suggest a matrix for the collection and structuring of information in order to report on the studied systems

Tailoring modal properties of inhibited-coupling guiding fibers by cladding modification

Understanding cladding properties is crucial for designing microstructured optical fibers. This is particularly acute for Inhibited-Coupling guiding fibers because of the reliance of their core guidance on the core and cladding mode-field overlap integral. Consequently, careful planning of the fiber cladding parameters allows obtaining fibers with optimized characteristics such as low loss and broad transmission bandwidth. In this manuscript, we report on how one can tailor the modal properties of hollow-core photonic crystal fibers by adequately modifying the fiber cladding. We show that the alteration of the position of the tubular fibers cladding tubes can alter the loss hierarchy of the modes in these fibers, and exhibit salient polarization propriety. In this context, we present two fibers with different cladding structures which favor propagation of higher order core modes \u2013 namely LP11 and LP21 modes. Additionally, we provide discussions on mode transformations in these fibers and show that one can obtain uncommon intensity and polarization profiles at the fiber output. This allows the fiber to act as a mode intensity and polarization shaper. We envisage this novel concept can be useful for a variety of applications such as hollow core fiber based atom optics, atom-surface physics, sensing and nonlinear optics

Controlled assembly of SNAP-PNA-fluorophore systems on DNA templates to produce fluorescence resonance energy transfer

The SNAP protein is a widely used self-labeling tag that can be used for tracking protein localization and trafficking in living systems. A model system providing controlled alignment of SNAP-tag units can provide a new way to study clustering of fusion proteins. In this work, fluorescent SNAP-PNA conjugates were controllably assembled on DNA frameworks forming dimers, trimers, and tetramers. Modification of peptide nucleic acid (PNA) with the O6-benzyl guanine (BG) group allowed the generation of site-selective covalent links between PNA and the SNAP protein. The modified BG-PNAs were labeled with fluorescent Atto dyes and subsequently chemo-selectively conjugated to SNAP protein. Efficient assembly into dimer and oligomer forms was verified via size exclusion chromatography (SEC), electrophoresis (SDS-PAGE), and fluorescence spectroscopy. DNA directed assembly of homo- and hetero-dimers of SNAP-PNA constructs induced homo- and hetero-FRET, respectively. Longer DNA scaffolds controllably aligned similar fluorescent SNAP-PNA constructs into higher oligomers exhibiting homo-FRET. The combined SEC and homo-FRET studies indicated the 1:1 and saturated assemblies of SNAP-PNA-fluorophore:DNA formed preferentially in this system. This suggested a kinetic/stoichiometric model of assembly rather than binomially distributed products. These BG-PNA-fluorophore building blocks allow facile introduction of fluorophores and/or assembly directing moieties onto any protein containing SNAP. Template directed assembly of PNA modified SNAP proteins may be used to investigate clustering behavior both with and without fluorescent labels which may find use in the study of assembly processes in cells

Gating of aquaporins by heavy metals in Allium cepa L. epidermal cells

Changes in the water permeability, aquaporin (AQP) activity, of leaf cells were investigated in response to different heavy metals (Zn2+, Pb2+, Cd2+, Hg2+). The cell pressure probe experiments were performed on onion epidermal cells as a model system. Heavy metal solutions at different concentrations (0.05 μM–2 mM) were used in our experiments. We showed that the investigated metal ions can be arranged in order of decreasing toxicity (expressed as a decrease in water permeability) as follows: Hg>Cd>Pb>Zn. Our results showed that β-mercaptoethanol treatment (10 mM solution) partially reverses the effect of AQP gating. The magnitude of this reverse differed depending on the metal and its concentration. The time course studies of the process showed that the gating of AQPs occurred within the first 10 min after the application of a metal. We also showed that after 20–40 min from the onset of metal treatment, the water flow through AQPs stabilized and remained constant. We observed that irrespective of the metal applied, the effect of AQP gating can be recorded within the first 10 min after the administration of metal ions. More generally, our results indicate that the toxic effects of investigated metal ions on the cellular level may involve AQP gating