111 research outputs found

    Convex Cycle Bases

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    Convex cycles play a role e.g. in the context of product graphs. We introduce convex cycle bases and describe a polynomial-time algorithm that recognizes whether a given graph has a convex cycle basis and provides an explicit construction in the positive case. Relations between convex cycles bases and other types of cycles bases are discussed. In particular we show that if G has a unique minimal cycle bases, this basis is convex. Furthermore, we characterize a class of graphs with convex cycles bases that includes partial cubes and hence median graphs. (authors' abstract)Series: Research Report Series / Department of Statistics and Mathematic

    A role for Insulin-like growth factor 2 in specification of the fast skeletal muscle fibre

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    <p>Abstract</p> <p>Background</p> <p>Fibre type specification is a poorly understood process beginning in embryogenesis in which skeletal muscle myotubes switch myosin-type to establish fast, slow and mixed fibre muscle groups with distinct function. Growth factors are required to establish slow fibres; it is unknown how fast twitch fibres are specified. Igf-2 is an embryonically expressed growth factor with established <it>in vitro </it>roles in skeletal muscle. Its localisation and role in embryonic muscle differentiation had not been established.</p> <p>Results</p> <p>Between E11.5 and E15.5 fast Myosin (FMyHC) localises to secondary myotubes evenly distributed throughout the embryonic musculature and gradually increasing in number so that by E15.5 around half contain FMyHC. The Igf-2 pattern closely correlates with FMyHC from E13.5 and peaks at E15.5 when over 90% of FMyHC+ myotubes also contain Igf-2. Igf-2 lags FMyHC and it is absent from muscle myotubes until E13.5. Igf-2 strongly down-regulates by E17.5. A striking feature of the FMyHC pattern is its increased heterogeneity and attenuation in many fibres from E15.5 to day one after birth (P1). Transgenic mice (MIG) which express Igf-2 in all of their myotubes, have increased FMyHC staining, a higher proportion of FMyHC+ myotubes and loose their FMyHC staining heterogeneity. In Igf-2 deficient mice (MatDi) FMyHC+ myotubes are reduced to 60% of WT by E15.5. <it>In vitro</it>, MIG induces a 50% excess of FMyHC+ and a 30% reduction of SMHyC+ myotubes in C2 cells which can be reversed by Igf-2-targeted ShRNA resulting in 50% reduction of FMyHC. Total number of myotubes was not affected.</p> <p>Conclusion</p> <p>In WT embryos the appearance of Igf-2 in embryonic myotubes lags FMyHC, but by E15.5 around 45% of secondary myotubes contain both proteins. Forced expression of Igf-2 into all myotubes causes an excess, and absence of Igf-2 suppresses, the FMyHC+ myotube component in both embryonic muscle and differentiated myoblasts. Igf-2 is thus required, not for initiating secondary myotube differentiation, but for establishing the correct proportion of FMyHC+ myotubes during fibre type specification (E15.5 - P1). Since specific loss of FMyHC fibres is associated with many skeletal muscle pathologies these data have important medical implications.</p

    Graph Laplacians, Nodal Domains, and Hyperplane Arrangements

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    Eigenvectors of the Laplacian of a graph G have received increasing attention in the recent past. Here we investigate their so-called nodal domains, i.e. the connected components of the maximal induced subgraphs of G on which an eigenvector ψ does not change sign. An analogue of Courant's nodal domain theorem provides upper bounds on the number of nodal domains depending on the location of ψ in the spectrum. This bound, however, is not sharp in general. In this contribution we consider the problem of computing minimal and maximal numbers of nodal domains for a particular graph. The class of Boolean Hypercubes is discussed in detail. We find that, despite the simplicity of this graph class, for which complete spectral information is available, the computations are still non-trivial. Nevertheless, we obtained some new results and a number of conjectures

    A note on quasi-robust cycle bases

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    We investigate here some aspects of cycle bases of undirected graphs that allow the iterative construction of all elementary cycles. We introduce the concept of quasi-robust bases as a generalization of the notion of robust bases and demonstrate that a certain class of bases of the complete bipartite graphs K m,n with m,n _> 5 is quasi-robust but not robust. We furthermore disprove a conjecture for cycle bases of Cartesian product graphs

    Beiträge zur Geschichte des Landkreises Regensburg 37

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    Heimat gestern und heute III - 56 Arbeitsproben von 12 Autoren; darin: Detterbeck, Pius: Mei Häuserl, mei Goat´n (S. 3); Fendl, Josef, Herbst im Jura (bei Schönhofen), Die Jahreszeit der fünf Sinne, Terra incognita, Schlecht verteilt, Diplomatisch (S. 4-5); Heigl, Margot: Hoamat, Grod a Hausfrau, Liebeserklärung, "Bayernbild", "Blaue" Volksmusik, Glück, Zeit, Kloana Unterschied (S. 6-8); Hemrich, Hans: Dö staade Zeit, Abschied, olt (S. 9-10); Kraus, Josef: A Pferdl, Nie Altwerden, Die alt Mauer, Scho wieder (S. 11-16); Mühldorfer, Albert: Koa Arbat, Mia samma aa wea, Wöiltbürger, Sanierung, Landschaftsplanung, Versaamt is versaamt, Rest-WAA-heit (S. 17-18); Rosenmeier, Maria: Fortschritt, Oasn, Schauspieler, Menschn, Moral, Generationsproblem, Glockenklang, Walhalla - Ruhmestempel (S. 19-20); Seitz, Angelika: Regensburg, August 85, wintergedeck, spätaugust, i bin unschuldig, im Normalfall (S. 21-23); Stadler, Ali: Gestern war´s, Woaßt as no? (S. 24-25); Staudigl, Franz Xaver: Beratzhausener Skizzen, Friedhof, Ansichtskarte "Partie am Marktplatz", Allegorie? (S. 26-27); Weigert, Hans: Macha, Da Duillnbock (S. 28-30); Zenger, Georg: Blick ins Allerseelenland (S. 31

    Lactobacillus johnsonii N6.2 Mitigates the Development of Type 1 Diabetes in BB-DP Rats

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    BACKGROUND: The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. METHODOLOGY/PRINCIPAL: Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. CONCLUSIONS: It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data suggest that the gut and the gut microbiota are potential agents of influence in type 1 diabetes development. These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder

    Structure-function studies of an engineered scaffold protein derived from stefin A. I: Development of the SQM variant

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    Non-antibody scaffold proteins are used for a range of applications, especially the assessment of protein–protein interactions within human cells. The search for a versatile, robust and biologically neutral scaffold previously led us to design STM (stefin A triple mutant), a scaffold derived from the intracellular protease inhibitor stefin A. Here, we describe five new STM-based scaffold proteins that contain modifications designed to further improve the versatility of our scaffold. In a step-by-step approach, we introduced restriction sites in the STM open reading frame that generated new peptide insertion sites in loop 1, loop 2 and the N-terminus of the scaffold protein. A second restriction site in ‘loop 2’ allows substitution of the native loop 2 sequence with alternative oligopeptides. None of the amino acid changes interfered significantly with the folding of the STM variants as assessed by circular dichroism spectroscopy. Of the five scaffold variants tested, one (stefin A quadruple mutant, SQM) was chosen as a versatile, stable scaffold. The insertion of epitope tags at varying positions showed that inserts into loop 1, attempted here for the first time, were generally well tolerated. However, N-terminal insertions of epitope tags in SQM had a detrimental effect on protein expression

    International Journal of Cancer / Synergistic crosstalk of hedgehog and interleukin6 signaling drives growth of basal cell carcinoma

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    Persistent activation of hedgehog (HH)/GLI signaling accounts for the development of basal cell carcinoma (BCC), a very frequent nonmelanoma skin cancer with rising incidence. Targeting HH/GLI signaling by approved pathway inhibitors can provide significant therapeutic benefit to BCC patients. However, limited response rates, development of drug resistance, and severe side effects of HH pathway inhibitors call for improved treatment strategies such as rational combination therapies simultaneously inhibiting HH/GLI and cooperative signals promoting the oncogenic activity of HH/GLI. In this study, we identified the interleukin6 (IL6) pathway as a novel synergistic signal promoting oncogenic HH/GLI via STAT3 activation. Mechanistically, we provide evidence that signal integration of IL6 and HH/GLI occurs at the level of cisregulatory sequences by cobinding of GLI and STAT3 to common HHIL6 target gene promoters. Genetic inactivation of Il6 signaling in a mouse model of BCC significantly reduced in vivo tumor growth by interfering with HH/GLIdriven BCC proliferation. Our genetic and pharmacologic data suggest that combinatorial HHIL6 pathway blockade is a promising approach to efficiently arrest cancer growth in BCC patients.(VLID)301234

    Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

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    In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article
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