334 research outputs found

    A Characterization of Undirected Graphs Admitting Optimal Cost Shares

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    In a seminal paper, Chen, Roughgarden and Valiant studied cost sharing protocols for network design with the objective to implement a low-cost Steiner forest as a Nash equilibrium of an induced cost-sharing game. One of the most intriguing open problems to date is to understand the power of budget-balanced and separable cost sharing protocols in order to induce low-cost Steiner forests. In this work, we focus on undirected networks and analyze topological properties of the underlying graph so that an optimal Steiner forest can be implemented as a Nash equilibrium (by some separable cost sharing protocol) independent of the edge costs. We term a graph efficient if the above stated property holds. As our main result, we give a complete characterization of efficient undirected graphs for two-player network design games: an undirected graph is efficient if and only if it does not contain (at least) one out of few forbidden subgraphs. Our characterization implies that several graph classes are efficient: generalized series-parallel graphs, fan and wheel graphs and graphs with small cycles.Comment: 60 pages, 69 figures, OR 2017 Berlin, WINE 2017 Bangalor

    An introduction to low-level analysis methods of DNA microarray data

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    This article gives an overview over the methods used in the low--level analysis of gene expression data generated using DNA microarrays. This type of experiment allows to determine relative levels of nucleic acid abundance in a set of tissues or cell populations for thousands of transcripts or loci simultaneously. Careful statistical design and analysis are essential to improve the efficiency and reliability of microarray experiments throughout the data acquisition and analysis process. This includes the design of probes, the experimental design, the image analysis of microarray scanned images, the normalization of fluorescence intensities, the assessment of the quality of microarray data and incorporation of quality information in subsequent analyses, the combination of information across arrays and across sets of experiments, the discovery and recognition of patterns in expression at the single gene and multiple gene levels, and the assessment of significance of these findings, considering the fact that there is a lot of noise and thus random features in the data. For all of these components, access to a flexible and efficient statistical computing environment is an essential aspect

    The characterization of the Pex11 protein family in yeast

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    Eukaryotische Organismen bestehen aus unterschiedlichen Kompartimenten. Diese sogenannten Organellen haben eine bestimmte Funktion in der Zelle. Sie sind von Membranen umgeben, die dafür sorgen, dass jedes Kompartiment seine Funktion ausüben kann. Peroxisomen spielen eine wichtige Rolle im Lipidmetabolismus. Sie sind sehr vielfältige Organellen, deren Größe, Zahl und Proteingehalt abhängig vom Zell- und Gewebetyp und von den Umweltbedingungen sind. Peroxisomen können durch Wachstum und Teilung aus bereits existierenden Organellen oder de novo aus dem endoplasmatischen Retikulum entstehen. Ihre Biogenese wird durch eine Gruppe von Proteinen, den sogenannten Peroxinen kontrolliert. In dieser Arbeit habe ich untersucht, wie sich Peroxisomen vermehren und welche Peroxine an diesem Prozess beteiligt sind. Die Hefe Saccharomyces cerevisiae wurde dabei als Modelorganismus benutzt. In diesem Organismus sind die Peroxine der Pex11 Proteinfamilie, Pex11p, Pex25p und Pex27p, in die Vermehrung der Peroxisomen involviert. Orthologe dieser Proteine wurden in allen eukaryotischen Organismen identifiziert. Hefezellen, denen PEX11 fehlt, besitzen weniger und größere Peroxisomen und konsumieren weniger Ölsäure als Wildtypzellen. Die detaillierte molekulare Funktion der Mitglieder der Pex11 Proteinfamilie war bis jetzt nicht bekannt. Das Ziel dieser Studie war es, die individuellen Rollen der drei Pex11-ähnlichen Hefeproteine zu bestimmen. Die Ergebnisse dieser Studie zeigen, dass Pex25p die Elongation der Membran bereits existierender Peroxisomen initiiert und an der de novo Biogenese aus dem ER beteiligt ist. Weiters bringe ich den Beweis, dass Pex27p eine inhibitorische oder kompetetive Rolle in der Aktivierung der Membranelongation von Peroxisomen spielt, aber auch die de novo Biogenese aus dem ER initiieren kann. Schließlich führen die Ergebnisse meiner Arbeit zur Schlussfolgerung, dass die Funktion von Pex11p auf den Erhalt der metabolischen Aktivität und die Vermehrung bereits existierender Peroxisomen beschränkt ist.All eukaryotic organisms are subdivided into different compartments. These compartments, named organelles execute distinct functions in the cell and the surrounding membranes make sure that each compartment is able to fulfil this function. Among these organelles, peroxisomes play an important role in lipid metabolism. They are highly versatile compartments whose size, number and protein content can vary depending on the cell and tissue type and on the environmental conditions. Peroxisomes can derive from already existing organelles by growth and division or they can be formed de novo from the endoplasmic reticulum. Their biogenesis is controlled by a set of proteins, the peroxins. In this study I investigated how peroxisomes proliferate and which peroxins play important roles in this process using the yeast Saccharomyces cerevisiae as model system. In this organism the peroxins of the Pex11 protein family, Pex11p, Pex25p and Pex27p, are known to be involved in peroxisome proliferation, orthologs of these have been identified in all eukaryotic organisms. Yeast cells lacking PEX11 display fewer and larger peroxisomes as well as reduced utilization of oleic acid compared to wild type cells. The detailed molecular function of the yeast Pex11 protein family members was not yet known, and the aim of this study was to reveal the individual roles of the three yeast Pex11-related proteins. The data from this study demonstrate that Pex25p catalyzes the priming event for membrane elongation of existing peroxisomes and participates in the initiation of de novo biogenesis from the ER. Moreover, I provide evidence that Pex27p fulfils an inhibitory or competitive function in the priming event of peroxisome membrane elongation but by itself is able to initiate de novo biogenesis at the ER. Finally, the results of my work lead to the conclusion that the function of Pex11p is limited to sustaining the metabolic activity and to promote the proliferation of peroxisomes already present in the cell

    A Subtle Interplay Between Three Pex11 Proteins Shapes De Novo Formation and Fission of Peroxisomes

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    The organization of eukaryotic cells into membrane-bound compartments must be faithfully sustained for survival of the cell. A subtle equilibrium exists between the degradation and the proliferation of organelles. Commonly, proliferation is initiated by a membrane remodeling process. Here, we dissect the function of proteins driving organelle proliferation in the particular case of peroxisomes. These organelles are formed either through a growth and division process from existing peroxisomes or de novo from the endoplasmic reticulum (ER). Among the proteins involved in the biogenesis of peroxisomes, peroxins, members of the Pex11 protein family participate in peroxisomal membrane alterations. In the yeast Saccharomyces cerevisiae, the Pex11 family consists of three proteins, Pex11p, Pex25p and Pex27p. Here we demonstrate that yeast mutants lacking peroxisomes require the presence of Pex25p to regenerate this organelle de novo. We also provide evidence showing that Pex27p inhibits peroxisomal function and illustrate that Pex25p initiates elongation of the peroxisomal membrane. Our data establish that although structurally conserved each of the three Pex11 protein family members plays a distinct role. While ScPex11p promotes the proliferation of peroxisomes already present in the cell, ScPex25p initiates remodeling at the peroxisomal membrane and ScPex27p acts to counter this activity. In addition, we reveal that ScPex25p acts in concert with Pex3p in the initiation of de novo peroxisome biogenesis from the ER

    Nuclear envelope transmembrane proteins (NETs) that are up-regulated during myogenesis

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    BACKGROUND: The nuclear lamina is a protein meshwork lining the inner nuclear membrane, which contains a polymer of nuclear lamins associated with transmembrane proteins of the inner nuclear membrane. The lamina is involved in nuclear structure, gene expression, and association of the cytoplasmic cytoskeleton with the nucleus. We previously identified a group of 67 novel putative nuclear envelope transmembrane proteins (NETs) in a large-scale proteomics analysis. Because mutations in lamina proteins have been linked to several human diseases affecting skeletal muscle, we examined NET expression during differentiation of C2C12 myoblasts. Our goal was to identify new nuclear envelope and lamina components whose expression is coordinated with muscle differentiation. RESULTS: Using transcriptional microarray analysis, we found that expression of 6 of the NETs significantly increases during myoblast differentiation. We confirmed these results using quantitative RT-PCR, and furthermore, found that all 6 NETs are expressed at high levels in adult mouse skeletal muscle relative to 9 other tissues examined. Using epitope-tagged cDNAs, we determined that the 5 NETs we could analyze (NETs 9, 25, 32, 37 and 39) all target to the nuclear envelope in C2C12 cells. Furthermore, the 3 NETs that we could analyze by immunoblotting were highly enriched in nuclear envelopes relative to microsomal membranes purified from mouse liver. Database searches showed that 4 of the 6 up-regulated NETs contain regions of homology to proteins previously linked to signaling. CONCLUSION: This work identified 6 NETs that are predicted to have important functions in muscle development and/or maintenance from their expression patterns during myoblast differentiation and in mouse tissues. We confirmed that 5 of these NETs are authentic nuclear envelope proteins. Four members of this group have potential signaling functions at the NE, based on their sequence homologies

    Исследование процесса электронно-лучевой наплавки нержавеющей проволокой в условиях аддитивных технологий

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    Объектом исследования является наплавленные образцы, полученные методом электронно-лучевого наплавления в условиях аддитивных технологий. Цель работы – рассмотрение микроструктуры и измерение микротвердости нержавеющих образцов марки AISI 308L (ГОСТ 08Х18Н10Т) и 40Х13. В ходе исследования рассматривались образцы, полученные методом электронно-лучевого наплавления. В качестве основного материала выступали нержавеющие стали марки AISI 308L (ГОСТ 08Х18Н10Т) и 40Х13. Исследование макроструктуры образцов и измерение микротвердости производились при помощи светового микроскопа Axio Observer A1.m и микротвердомера DuraScan.The object of the study is the deposited samples obtained by the electron beam direction method under the conditions of additive technologies. The purpose of the work is to consider the microstructure and measure the microhardness of stainless samples of the AISI 308L (ГОСТ 08X18H10T) and 40X13 grades. In the course of the study, samples obtained by the electron beam direction method were considered. The main material was stainless steel AISI 308L (ГОСТ 08X18H10T) and 40X13. The macrostructure of the samples and the microhardness were studied using an Axio Observer A1.m light microscope and a DuraScan microhardness meter

    EEG Sleep Slow-Wave Activity as a Mirror of Cortical Maturation

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    Deep (slow wave) sleep shows extensive maturational changes from childhood through adolescence, which is reflected in a decrease of sleep depth measured as the activity of electroencephalographic (EEG) slow waves. This decrease in sleep depth is paralleled by massive synaptic remodeling during adolescence as observed in anatomical studies, which supports the notion that adolescence represents a sensitive period for cortical maturation. To assess the relationship between slow-wave activity (SWA) and cortical maturation, we acquired sleep EEG and magnetic resonance imaging data in children and adolescents between 8 and 19 years. We observed a tight relationship between sleep SWA and a variety of indexes of cortical maturation derived from magnetic resonance (MR) images. Specifically, gray matter volumes in regions correlating positively with the activity of slow waves largely overlapped with brain areas exhibiting an age-dependent decrease in gray matter. The positive relationship between SWA and cortical gray matter was present also for power in other frequency ranges (theta, alpha, sigma, and beta) and other vigilance states (theta during rapid eye movement sleep). Our findings indicate a strong relationship between sleep EEG activity and cortical maturation. We propose that in particular, sleep SWA represents a good marker for structural changes in neuronal networks reflecting cortical maturation during adolescenc

    Photodynamic Inactivation of Bacteria in Ionic Environments Using the Photosensitizer SAPYR and the Chelator Citrate

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    Many studies show that photodynamic inactivation (PDI) is a powerful tool for the fight against pathogenic, multiresistant bacteria and the closing of hygiene gaps. However, PDI studies have been frequently performed under standardized in vitro conditions comprising artificial laboratory settings. Under real-life conditions, however, PDI encounters substances like ions, proteins, amino acids and fatty acids, potentially hampering the efficacy of PDI to an unpredictable extent. Thus, we investigated PDI with the phenalene-1-one-based photosensitizer SAPYR against Escherichia coli and Staphylococcus aureus in the presence of calcium or magnesium ions, which are ubiquitous in potential fields of PDI applications like in tap water or on tissue surfaces. The addition of citrate should elucidate the potential as a chelator. The results indicate that PDI is clearly affected by such ubiquitous ions depending on its concentration and the type of bacteria. The application of citrate enhanced PDI, especially for Gram-negative bacteria at certain ionic concentrations (e.g. CaCl2 or MgCl2: 7.5 to 75 mmol L−1). Citrate also improved PDI efficacy in tap water (especially for Gram-negative bacteria) and synthetic sweat solution (especially for Gram-positive bacteria). In conclusion, the use of chelating agents like citrate may facilitate the application of PDI under real-life conditions
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