Deep-learning based segmentation of challenging myelin sheaths

The segmentation of axons and myelin in electron microscopy images allows neurologists to highlight the density of axons and the thickness of the myelin surrounding them. These properties are of great interest for preventing and anticipating white matter diseases. This task is generally performed manually, which is a long and tedious process. We present an update of the methods used to compute that segmentation via machine learning. Our model is based on the architecture of the U-Net network. Our main contribution consists in using transfer learning in the encoder part of the UNet network, as well as test time augmentation when segmenting. We use the SE-Resnet50 backbone weights which was pre-trained on the ImageNet 2012 dataset. We used a data set of 23 images with the corresponding segmented masks, which also was challenging due to its extremely small size. The results show very encouraging performances compared to the state-of-the-art with an average precision of 92% on the test images. It is also important to note that the available samples were taken from elderly mices in the corpus callosum. This represented an additional difficulty, compared to related works that had samples taken from the spinal cord or the optic nerve of healthy individuals, with better contours and less debri

Membrane permeation of arginine-rich cell-penetrating peptides independent of transmembrane potential as a function of lipid composition and membrane fluidity

Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration. However, the molecular parameters underlying this import mechanism are still poorly defined. Here, we make use of the frequently used HeLa and HEK cell lines to address the role of lipid composition and membrane potential. In HeLa cells, at low concentrations, the CPP nona-arginine (R9) enters cells by endocytosis. Direct membrane penetration occurs only at high peptide concentrations through a mechanism involving activation of sphingomyelinase which converts sphingomyelin into ceramide. In HEK cells, by comparison, R9 enters the cytoplasm through direct membrane permeation already at low concentrations. This direct permeation is strongly reduced at room temperature and upon cholesterol depletion, indicating a complex dependence on membrane fluidity and microdomain organisation. Lipidomic analyses show that in comparison to HeLa cells HEK cells have an endogenously low sphingomyelin content. Interestingly, direct permeation in HEK cells and also in HeLa cells treated with exogenous sphingomyelinase is independent of membrane potential. Membrane potential is only required for induction of sphingomyelinase-dependent uptake which is then associated with a strong hyperpolarization of membrane potential as shown by whole-cell patch clamp recordings. Next to providing new insights into the interplay of membrane composition and direct permeation, these results also refute the long-standing paradigm that transmembrane potential is a driving force for CPP uptake

Modified Quark-Meson Coupling Model for Nuclear Matter

The quark-meson coupling model for nuclear matter, which describes nuclear matter as non-overlapping MIT bags bound by the self-consistent exchange of scalar and vector mesons, is modified by introducing medium modification of the bag constant. We model the density dependence of the bag constant in two different ways: one invokes a direct coupling of the bag constant to the scalar meson field, and the other relates the bag constant to the in-medium nucleon mass. Both models feature a decreasing bag constant with increasing density. We find that when the bag constant is significantly reduced in nuclear medium with respect to its free-space value, large canceling isoscalar Lorentz scalar and vector potentials for the nucleon in nuclear matter emerge naturally. Such potentials are comparable to those suggested by relativistic nuclear phenomenology and finite-density QCD sum rules. This suggests that the reduction of bag constant in nuclear medium may play an important role in low- and medium-energy nuclear physics.Comment: Part of the text is reordered, revised version to appear in Phys. Rev. C. 19 pages, ReVTeX, 4 figures embedde

Collective modes of asymmetric nuclear matter in Quantum HadroDynamics

We discuss a fully relativistic Landau Fermi liquid theory based on the Quantum Hadro-Dynamics ($QHD$) effective field picture of Nuclear Matter ({\it NM}). From the linearized kinetic equations we get the dispersion relations of the propagating collective modes. We focus our attention on the dynamical effects of the interplay between scalar and vector channel contributions. A beautiful ``mirror'' structure in the form of the dynamical response in the isoscalar/isovector degree of freedom is revealed, with a complete parallelism in the role respectively played by the compressibility and the symmetry energy. All that strongly supports the introduction of an explicit coupling to the scalar-isovector channel of the nucleon-nucleon interaction. In particular we study the influence of this coupling (to a $\delta$-meson-like effective field) on the collective response of asymmetric nuclear matter ($ANM$). Interesting contributions are found on the propagation of isovector-like modes at normal density and on an expected smooth transition to isoscalar-like oscillations at high baryon density. Important ``chemical'' effects on the neutron-proton structure of the mode are shown. For dilute $ANM$ we have the isospin distillation mechanism of the unstable isoscalar-like oscillations, while at high baryon density we predict an almost pure neutron wave structure of the propagating sounds.Comment: 18 pages (LATEX), 8 Postscript figures, uses "epsfig

omega-nucleus bound states in the Walecka model

Using the Walecka model, we investigate theoretically whether an omega meson is bound to finite nuclei. We study several nuclei from ^{6}He to ^{208}Pb, and compare the results with those in the quark-meson coupling (QMC) model. Our calculation shows that deeper omega-nucleus bound states are predicted in the Walecka model than in QMC. One can expect to detect such bound states in the proposed experiment involving the (d,^3He) reaction at GSI.Comment: 11 pages, including 2 ps files and 2 table

Dispersion relation of the ρ\rho meson in hot/dense nuclear matter

The dispersion relation of $\rho$ meson in both timelike and spacelike regimes in hot and dense nuclear medium is analyzed and compared with $\sigma$ meson based on the quantum hadrodynamics model. The pole and screening masses of $\rho$ and $\sigma$ are discussed. The behavior of screening mass of $\rho$ is different from that of $\sigma$ due to different Dirac- and Fermi-sea contributions at finite temperature and density.Comment: 4 pages, 3 figures, identical to published versio

CpG-ODN and MPLA Prevent Mortality in a Murine Model of Post-Hemorrhage-Staphyloccocus aureus Pneumonia

Infections are the most frequent cause of complications in trauma patients. Post-traumatic immune suppression (IS) exposes patients to pneumonia (PN). The main pathogen involved in PN is Methicillin Susceptible Staphylococcus aureus (MSSA). Dendritic cells () may be centrally involved in the IS. We assessed the consequences of hemorrhage on pneumonia outcomes and investigated its consequences on DCs functions. A murine model of hemorrhagic shock with a subsequent MSSA pneumonia was used. Hemorrhage decreased the survival rate of infected mice, increased systemic dissemination of sepsis and worsened inflammatory lung lesions. The mRNA expression of Tumor Necrosis Factor-alpha (TNF-α), Interferon-beta (IFN-β) and Interleukin (IL)-12p40 were mitigated for hemorrhaged-mice. The effects of hemorrhage on subsequent PN were apparent on the pDCs phenotype (reduced MHC class II, CD80, and CD86 molecule membrane expression). In addition, hemorrhage dramatically decreased CD8+ cDCs- and CD8- cDCs-induced allogeneic T-cell proliferation during PN compared with mice that did not undergo hemorrhage. In conclusion, hemorrhage increased morbidity and mortality associated with PN; induced severe phenotypic disturbances of the pDCs subset and functional alterations of the cDCs subset. After hemorrhage, a preventive treatment with CpG-ODN or Monophosphoryl Lipid A increased transcriptional activity in DCs (TNF-α, IFN-β and IL-12p40) and decreased mortality of post-hemorrhage MSSA pneumonia

Corrigendum to 'Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections' [European Journal of Vascular & Endovascular Surgery 59/3 (2020) 339-384]

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