326,564 research outputs found
Differential expression and MAL-dependent targeting of the L-MAG and S-MAG isoforms to myelin membranes
No full textMany degenerative diseases of the nervous system, including Multiple Sclerosis and peripheral neuropathies, are triggered by an impaired interaction between the axons and their surrounding myelin sheaths. The cause for this disturbed axon-myelin interaction, and the secondary neuronal damage that produces the clinical symptoms, lies in a primary defect of the myelin sheath. The myelin sheath itself is formed and maintained by oligodendrocytes and Schwann cells, the myelinating glial cells of the central and peripheral nervous system, respectively. The isoforms of the myelin-associated glycoprotein (MAG) are thought to be potential key elements of axon-myelin interaction, since these immunoglobulin-like cell signalling proteins are known to be localized in the periaxonal and paranodal myelin membranes. The MAG isoforms each display one of two possible intracellular C-termini as a result of alternative mRNA splicing. The C-terminus of the large isoform (L-MAG) has been shown to mediate downstream signals via the non-receptor tyrosine kinase Fyn, while the Cterminus of the short isoform (S-MAG) is thought to interact with the glial cytoskeleton. We have investigated the regulation and differential expression of L- and S-MAG in oligodendroglial cells and in transgenic mice by the use of genomic constructs that encode individually green fluorescent protein-tagged MAG isoforms. In the oligodendroglial cells LMAG was the dominant isoform prior to the stimulation of cells with cyclicAMP, whereas upon cyclicAMP stimulation, S-MAG was predominantly expressed in cells exhibiting advanced morphological differentiation. The investigation of our transgenic mice revealed that the two MAG isoforms are differentially expressed in distinct fibre tracts of the striatum and that S-MAG seems to be predominantly expressed in the long projecting fibres of the corpus callosum. Thus, the two MAG isoforms appear not only to be differentially expressed during development and in the adult, but they seem to mediate isoform-specific aspects of the axon-myelin interaction in distinct regions of the adult brain. A major question in the formation and maintenance of the myelin-axon interaction concerns the coordinated targeting of myelin signalling molecules and lipids to the different myelin compartments. Recent results suggest that glycolipid-enriched microdomains, socalled 'lipid-rafts', are involved in special sorting and trafficking mechanisms of membrane proteins and lipids. Furthermore, they are thought to serve as platforms for signal transduction processes. This makes them to interesting candidates for axon-myelin interactions, as well as for interactions between the apposed myelin membranes. The integral membrane protein 'Myelin and Lymphocyte Protein' (MAL) is suggested to be involved in lipid-raft-mediated protein targeting and signalling in myelinating cells. Our investigation of adult brain tissue of MAL-deficient mice showed that the incorporation of particular myelin components, such as MAG, into myelin membranes was significantly reduced. Thus, the targeting of L- and S-MAG to the myelin membranes appears to be dependent on the lipid-raft protein MAL. Furthermore, the MAL-deficient mice showed several ultra structural alterations comparable to those of the MAG-deficient mice and that reflect an impaired axon-myelin interaction. Our data supports the idea that-raft mediated trafficking of myelin constituents, such as MAG, to the different myelin compartments is a major task of adult oligodendrocytes in the context of maintaining the axonal contact of the myelin sheath. With the use of the isoform specific tagged MAG expressing mice, it will be possible for the first time, to investigate their differential function in axon-glia interaction as well as their dependence on MAL in vivo
George S. Erb, Charter Member
No full textPortrait of George S. Erb, Charter Member of the Alta Club in Salt Lake City, Utah, hotel manager, managed the Walker and the Metropolitan hotel
The Application of Bone Histology for Species Identification in Archaeology; with a Photo Catalogue
No full textKars, H. [Promotor]Deschler-Erb, S. [Copromotor]Lauwerier, R.C.G.M. [Copromotor
Portrait of George S. Erb, Charter Member
No full textPortrait of George S. Erb, Charter Member of the Alta Club in Salt Lake City, Utah, hotel manager, managed the Walker and the Metropolitan hotel
An alternative to Slepian functions on the unit sphere - A space-frequency analysis based on localized spherical polynomials
No full textIn this article, we present a space-frequency theory for spherical harmonics based on the spectral decomposition of a particular space-frequency operator. The presented theory is closely linked to the theory of ultraspherical polynomials on the one hand, and to the theory of Slepian functions on the 2-sphere on the other. Results from both theories are used to prove localization and approximation properties of the new band-limited yet space-localized basis. Moreover, particular weak limits related to the structure of the spherical harmonics provide information on the proportion of basis functions needed to approximate localized functions. Finally, a scheme for the fast computation of the coefficients in the new localized basis is provided
Das frühkaiserzeitliche Militärlager in den Augster Unterstadt. Forschungen in Augst 12 Köln:Rheinland-Verlag GmbH ,1994
No full textItem does not contain fulltextE. Deschler-Erb Das frühkaiserzeitliche Militärlager in den Augster Unterstadt. Forschungen in Augst 12 Köln:Rheinland-Verlag GmbH ,199
[Rezension zu:] Phillippe DELLA CASA – Eckhard DESCHLER-ERB (Hgg.), Rome's Internal Frontiers. Proceedings of the 2016 RAC Session in Rome. Zurich Studies in Archaeology Bd. 11. Zürich: Chronos Verlag 2017, 180 S., 90 farb. Abb.
No full textVerbreitungsbilder von Artefakten regten die archäologische Forschung seit dem späten 19. Jahrhundert dazu an, "Kulturkreise" zu definieren und auf dieser Basis Siedlungsräume ethnischer Gruppen, deren (Fremd)bezeichnung in lateinischen und griechischen Schriftquellen überliefert ist, zu lokalisieren. Diese Herangehensweise provoziert seit nunmehr fast zwei Jahrzehnten eine heftige Diskussion über die Interpretierbarkeit materieller Quellen im Hinblick auf die Benennung, Definition und Lokalisierung antiker Ethnien und Identitäten. ...
Einem ganz anderen Sujet widmet sich der abschließende archäobiologische Beitrag "Searching for Rome’s boundaries: An archaeobiological perspective" von Sabine Deschler-Erb, die anhand des Tierknochenspektrums verschiedener Fundplätze im Dreieck zwischen Avenches, Bregenz und Chur der Frage des Einflusses naturräumlicher Faktoren im Tierknochenbestand und den daraus resultierenden Speisegewohnheiten nachgeht. ..
A Novel Fully Human Antitumor ImmunoRNase Targeting ErbB2-Positive Tumors
No full textA second generation anti-ErbB2 ImmunoRNase, called Erb-hcAb-RNase, was obtained by the fusion of Erb-hcAb, a human compact anti-ErbB2 antibody, with human pancreatic ribonuclease (HP-RNase or RNase 1).
We show herein that Erb-hcAb-RNase retains the enzymatic activity of human pancreatic RNase and specifically binds to ErbB2-positive cells with an affinity comparable to that of the parental Erb-hcAb. Moreover, this novel immunoRNase is endowed with an effective and selective antiproliferative action for ErbB2-positive tumor cells both in vitro and in vivo. Its antitumor activity is more potent than that of the parental Erb-hcAb as the novel immunoconjugate has acquired RNase-based cytotoxicity in addition to the inhibitory growth effects, antibody-dependent and complement-dependent cytotoxicity of the compact antibody.
Erb-hcAb-RNase could be a promising candidate for the immunotherapy of ErbB2-positive tumours as it combines the advantages of the first generation scFv-based immunoRNase with those of a fully functional antibod
Concurrent Optimization of Launcher Architectures and Ascent Trajectories with Global Optimization Algorithms
No full textIn the context of a research work conducted on multi-objective global optimization techniques, the paper presents their application to the combined optimization of launcher high level architecture and ascent trajectories. The applicative scenario has been developed in two steps: first, the trajectory optimization has been implemented for existing launchers with fixed design parameters, and then the launcher architecture has been introduced in the optimization cycle. The proposed high level architecture modelling is intended to provide a tool in the early stage of new conceptual design optimization and analysis for Earth or planetary launchers. Hence, the algorithms concentrate on the number, type, thrust and propellant mass of stages and boosters as optimization variables. The resulting search space is extremely vast and multi-modal, with a mixed continuous-discrete nature, making the global approach necessary. After a detailed comparison work of various optimization techniques, the well known NSGA-II (Non-dominated Sorting Genetic Algorithm-II) and a newly developed version of Particle Swarm Optimization method, called DG-MOPSO (Double-Grid Multi-Objective Particle Swarm Optimization), have been selected for the applicative scenario. The paper presents in detail the models, their validation and the results obtained for two applicative cases. Both the selected algorithms provide reliable ascent trajectory design results for several different target orbits, showing a non negligible advantage of DG-MOPSO over NSGA-II, and the validity of the developed architecture for the concurrent optimization of launcher architectures and ascent trajectories has been proved, though the parametric models need to be refined to obtain more realistic results. This work is to be intended as the first step towards a complete multi-disciplinary design optimization (MDO) approach, potentially capable of providing a versatile automatic launchers preliminary design environment
Kernel-based models for influence maximization on graphs based on Gaussian process variance minimization
No full textThe inference of novel knowledge, the discovery of hidden patterns, and the uncovering of insights from large amounts of data from a multitude of sources make data science to an art rather than just a mere scientific discipline. The study and design of mathematical models and signal processing tools able to analyze information represents a central research topic within data science. In this work, we introduce and investigate a model for influence maximization (IM) on graphs using ideas from kernel-based signal approximation, Gaussian process regression, and the minimization of a corresponding variance term. Data-driven approaches can be applied to determine proper kernels for this IM model and machine learning methodologies are adopted to tune the model parameters. Compared to stochastic models for influence maximization that rely on Monte-Carlo simulations, our kernel-based model allows for a simple and cost-efficient update strategy to compute optimal influencing nodes on a graph. In several numerical experiments, we show the properties and benefits of this model
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