Functional Dysregulations in CA1 Hippocampal Networks of a 3-Hit Mouse Model of Schizophrenia

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility—partial deletion of the MAP6 gene, early-life stress—maternal separation, and pharmacological treatment—chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABA_A receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.     

Combining Points and Tangents into Parabolic Polygons

Image and geometry processing applications estimate the local geometry of objects using information localized at points. They usually consider information about the tangents as a side product of the points coordinates. This work proposes parabolic polygons as a model for discrete curves, which intrinsically combines points and tangents. This model is naturally affine invariant, which makes it particularly adapted to computer vision applications. As a direct application of this affine invariance, this paper introduces an affine curvature estimator that has a great potential to improve computer vision tasks such as matching and registering. As a proof-of-concept, this work also proposes an affine invariant curve reconstruction from point and tangent data.     

Immunoaffinity-chromatography purification of salbutamol in liver and HPLC-fluorometric detection at trace residue level

Summary A method combining immunoaffmity-chromatography (IAC) and high-performance liquid chromatography (HPLC) for the analysis of Salbutamol in liver with a low quantification limit of 1 g/kg has been developed. Salbutamol was extracted with 0.01 mol/L HCl and purified by IAC. The samples were analysed on a liquid Chromatograph fitted with a C₁₈ -Bondapak column. A fluorometer was used for the detection of salbutamol. Recoveries of 67–80% could be obtained.

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Immunoaffinitätschromatographische Reinigung von Salbutamol in Leber und Rückstandsbestimmung mittels HPLC und fluorimetrischer Detektion

Zusammenfassung Eine Methode, die Immunoaffinitäts-und Hochleistungsflüssigchromatographie verbindet, ist für die Analyse von Salbutamol in Leber entwickelt worden. Eine niedrige Bestimmungsgrenze von 1 g/kg Leber wurde erreicht. Salbutamol wurde mit 0,01 mol/L Salzsäure freigesetzt und durch Immunoaffinitätschromatographie gereinigt. Die Proben wurden durch Flüssigchromatographie auf einer C₁₈ -Bondapak-Säule analysiert. Ein Fluorimeter wurde für die Detektion von Salbutamol benutzt. Ausbeuten von 67 bis 80% konnten erreicht werden.

     

The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.     

Boosting MUC extraction in unsatisfiable constraint networks

One very fertile domain of applied Artificial Intelligence is constraint solving technologies. Especially, constraint networks that concern problems that can be represented using discrete variables, together with constraints on allowed instantiation values for these variables. Every solution to a constraint network must satisfy every constraint. When no solution exists, the user might want to know the actual reasons leading to the absence of global solution. In this respect, extracting mucs (Minimal Unsatisfiable Cores) from an unsatisfiable constraint network is a useful process when causes of unsatisfiability must be understood so that the network can be re-engineered and relaxed to become satisfiable. Despite bad worst-case computational complexity results, various muc-finding approaches that appear tractable for many real-life instances have been proposed. Many of them are based on the successive identification of so-called transition constraints. In this respect, we show how local search can be used to possibly extract additional transition constraints at each main iteration step. In the general constraint networks setting, the approach is shown to outperform a technique based on a form of model rotation imported from the sat-related technology and that also exhibits additional transition constraints. Our extensive computational experimentations show that this enhancement also boosts the performance of state-of-the-art DC(WCORE)-like MUC extractors.     

Sparse Non-negative Stencils for Anisotropic Diffusion

We introduce a new discretization scheme for Anisotropic Diffusion, AD-LBR, on two and three dimensional Cartesian grids. The main features of this scheme is that it is non-negative and has sparse stencils, of cardinality bounded by 6 in 2D, by 12 in 3D, despite allowing diffusion tensors of arbitrary anisotropy. The radius of these stencils is not a-priori bounded however, and can be quite large for pronounced anisotropies. Our scheme also has good spectral properties, which permits larger time steps and avoids e.g. chessboard artifacts. AD-LBR relies on Lattice Basis Reduction, a tool from discrete mathematics which has recently shown its relevance for the discretization on grids of strongly anisotropic Partial Differential Equations (Mirebeau in Preprint, 2012). We prove that AD-LBR is in 2D asymptotically equivalent to a finite element discretization on an anisotropic Delaunay triangulation, a procedure more involved and computationally expensive. Our scheme thus benefits from the theoretical guarantees of this procedure, for a fraction of its cost. Numerical experiments in 2D and 3D illustrate our results.     

Polypropylene/polyamide 6/polyethylene-octene elastomer blends. Part 3. Mechanisms of volume dilatation during plastic deformation under uniaxial tension

It has been shown in a previous paper in this series that important dilatation is produced by plastic deformation under tension of neat PP and PP/PA6/POE blends, for which the POE to PA6 concentration ratio equals 1/2. In this work, the detailed mechanisms of this volume change are investigated from electron micrographs (SEM and TEM) obtained in the deformed state. At low alloy content, it is thus observed that dilatation results from decohesion of the PA6 particles from the PP matrix. As the amount of PA6 and POE increases, voids are nucleated preferentially in the thicker POE interphase making a shell around the PA6 particles, and secondarily in isolated POE particles. Unexpectedly, it has been found that the overall volume dilatation decreases with total alloying content. This is interpreted by: (i) the increasing contribution of PA6 that intrinsically deforms with less cavitation than PP, (ii) the post-cavitation rubber-like stretching of POE particles and, (iii) the early formation of a percolating network of shear bands from the diffuse array of voids formed after the yield point. These mechanisms explain the gradual increase of the resistance to impact of the PP/PA6/POE as their alloying content is increased.     

Exploring factors related to users’ experience of public transport route choice: influence of context and users profiles

This exploratory study aims to achieve a better understanding of the users-related factors that affect the choice of routes in public transport (PT). We also look at what can motivate route and modes changes towards alternatives in a real situation. We investigated the experience of 19 users of PTs, using the critical incident technique (Flanagan in Psychol Bull 51(4):327, 1954). We asked participants to report incidents (i.e. situations) in cases they were very satisfied or dissatisfied with their choice. For both situations, the case of their usual route and case of an alternative were considered. A total of 91 incidents were collected and analysed using a multiple correspondences analysis. Additionally, users’ profiles were characterized and superposed to the analysis of incidents content. The main results are as follows. First, the user’s choice of PT route depends on the context (i.e. aim of the travel, time of day). Second, taking an alternative to the usual PT route or using a route combining different transport modes is determined by the context and by factors related to the pleasantness of the travel (e.g. to accompany a friend along the travel). Finally, depending on the user’s profile (i.e. combination of attitude towards PT and demographic variables), the factors taken into account to make the choice of a PT route are related to the efficiency or the pleasantness of the trip. These results show the importance of the contextual factors and the users’ profiles in route choice. They suggest that these factors should be further taken into account in new tools and services for mobility.     

CADNA: a library for estimating round-off error propagation

The CADNA library enables one to estimate round-off error propagation using a probabilistic approach. With CADNA the numerical quality of any simulation program can be controlled. Furthermore by detecting all the instabilities which may occur at run time, a numerical debugging of the user code can be performed. CADNA provides new numerical types on which round-off errors can be estimated. Slight modifications are required to control a code with CADNA, mainly changes in variable declarations, input and output. This paper describes the features of the CADNA library and shows how to interpret the information it provides concerning round-off error propagation in a code.

Program summary

Program title:CADNACatalogue identifier:AEAT_v1_0Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEAT_v1_0.htmlProgram obtainable from:CPC Program Library, Queen's University, Belfast, N. IrelandLicensing provisions:Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.htmlNo. of lines in distributed program, including test data, etc.:53 420No. of bytes in distributed program, including test data, etc.:566 495Distribution format:tar.gzProgramming language:FortranComputer:PC running LINUX with an i686 or an ia64 processor, UNIX workstations including SUN, IBMOperating system:LINUX, UNIXClassification:4.14, 6.5, 20Nature of problem:A simulation program which uses floating-point arithmetic generates round-off errors, due to the rounding performed at each assignment and at each arithmetic operation. Round-off error propagation may invalidate the result of a program. The CADNA library enables one to estimate round-off error propagation in any simulation program and to detect all numerical instabilities that may occur at run time.Solution method:The CADNA library [1] implements Discrete Stochastic Arithmetic [2-4] which is based on a probabilistic model of round-off errors. The program is run several times with a random rounding mode generating different results each time. From this set of results, CADNA estimates the number of exact significant digits in the result that would have been computed with standard floating-point arithmetic.Restrictions:CADNA requires a Fortran 90 (or newer) compiler. In the program to be linked with the CADNA library, round-off errors on complex variables cannot be estimated. Furthermore array functions such as product or sum must not be used. Only the arithmetic operators and the abs, min, max and sqrt functions can be used for arrays.Running time:The version of a code which uses CADNA runs at least three times slower than its floating-point version. This cost depends on the computer architecture and can be higher if the detection of numerical instabilities is enabled. In this case, the cost may be related to the number of instabilities detected.References:

[1]

The CADNA library, URL address: http://www.lip6.fr/cadna.

[2]

J.-M. Chesneaux, L'arithmétique Stochastique et le Logiciel CADNA, Habilitation á diriger des recherches, Université Pierre et Marie Curie, Paris, 1995.

[3]

J. Vignes, A stochastic arithmetic for reliable scientific computation, Math. Comput. Simulation 35 (1993) 233-261.

[4]

J. Vignes, Discrete stochastic arithmetic for validating results of numerical software, Numer. Algorithms 37 (2004) 377-390.

     

Anisotropic Smoothness Classes: From Finite Element Approximation to Image Models

We propose and study quantitative measures of smoothness f ? A(f) which are adapted to anisotropic features such as edges in images or shocks in PDE’s. These quantities govern the rate of approximation by adaptive finite elements, when no constraint is imposed on the aspect ratio of the triangles, the simplest example being \(A_{p}(f)=\|\sqrt{|\mathrm{det}(d^{2}f)|}\|_{L^{\tau}}\) which appears when approximating in the L ^p norm by piecewise linear elements when \(\frac{1}{\tau}=\frac{1}{p}+1\). The quantities A(f) are not semi-norms, and therefore cannot be used to define linear function spaces. We show that these quantities can be well defined by mollification when f has jump discontinuities along piecewise smooth curves. This motivates for using them in image processing as an alternative to the frequently used total variation semi-norm which does not account for the smoothness of the edges.