Power quality monitoring data management and analysis for distribution networks

publishedVersionPeer reviewe

Spherical structures on torus knots and links

The present paper considers two infinite families of cone-manifolds endowed with spherical metric. The singular strata is either the torus knot ${\rm t}(2n+1, 2)$ or the torus link ${\rm t}(2n, 2)$. Domains of existence for a spherical metric are found in terms of cone angles and volume formul{\ae} are presented.Comment: 17 pages, 5 figures; typo

A hypercyclic finite rank perturbation of a unitary operator

A unitary operator $V$ and a rank $2$ operator $R$ acting on a Hilbert space \H are constructed such that $V+R$ is hypercyclic. This answers affirmatively a question of Salas whether a finite rank perturbation of a hyponormal operator can be supercyclic.Comment: published in Mathematische Annale

TGF-β-induced growth inhibition in B-cell lymphoma correlates with Smad1/5 signalling and constitutively active p38 MAPK

<p>Abstract</p> <p>Background</p> <p>Cytokines of the transforming growth factor β (TGF-β) superfamily exert effects on proliferation, apoptosis and differentiation in various cell types. Cancer cells frequently acquire resistance to the anti-proliferative signals of TGF-β, which can be due to mutations in proteins of the signalling cascade. We compared the TGF-β-related signalling properties in B-cell lymphoma cell lines that were sensitive or resistant to TGF-β-induced anti-proliferative effects.</p> <p>Results</p> <p>TGF-β sensitive cell lines expressed higher cell surface levels of the activin receptor-like kinase 5 (Alk-5), a TGF-β receptor type 1. The expression levels of the other TGF-β and bone morphogenetic protein receptors were comparable in the different cell lines. TGF-β-induced phosphorylation of Smad2 was similar in TGF-β sensitive and resistant cell lines. In contrast, activation of Smad1/5 was restricted to cells that were sensitive to growth inhibition by TGF-β. Moreover, with activin A we detected limited anti-proliferative effects, strong phosphorylation of Smad2, but no Smad1/5 phosphorylation. Up-regulation of the TGF-β target genes Id1 and Pai-1 was identified in the TGF-β sensitive cell lines. Constitutive phosphorylation of MAPK p38 was restricted to the TGF-β sensitive cell lines. Inhibition of p38 MAPK led to reduced sensitivity to TGF-β.</p> <p>Conclusions</p> <p>We suggest that phosphorylation of Smad1/5 is important for the anti-proliferative effects of TGF-β in B-cell lymphoma. Alk-5 was highly expressed in the sensitive cell lines, and might be important for signalling through Smad1/5. Our results indicate a role for p38 MAPK in the regulation of TGF-β-induced anti-proliferative effects.</p

TFPIα Interacts with FVa and FXa to Inhibit Prothrombinase During the Initiation of Coagulation

Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry. Removal of FXa active site binding by mutation or by deletion of the second Kunitz domain (K2) of TFPIα produced 17- or 34-fold weaker prothrombinase inhibition, respectively, establishing that K2 binding to the FXa active site is required for efficient inhibition. Substitution of the TFPIα basic region uncharged residues (Leu252, Ile253, Thr255) with Ala (TFPI-AAKA) produced 5.8-fold decreased inhibition. This finding was confirmed using a basic region peptide (Leu252-Lys261) and Ala substitution peptides, which established that the uncharged residues are required for prothrombinase inhibitory activity but not for binding the FVa acidic region. This suggests that the uncharged residues mediate a secondary interaction with FVa subsequent to acidic region binding. This secondary interaction seems to be with the FVa heavy chain, because the FV Leiden mutation weakened prothrombinase inhibition by TFPIα but did not alter TFPI-AAKA inhibitory activity. Thus, efficient inhibition of prothrombinase by TFPIα requires at least 3 intermolecular interactions: (1) the TFPIα basic region binds the FVa acidic region, (2) K2 binds the FXa active site, and (3) Leu252-Thr255 binds the FVa heavy chain

A comparison between the homocyclic aromatic metabolic pathways from plant-derived compounds by bacteria and fungi

Aromatic compounds derived from lignin are of great interest for renewable biotechnical applications. They can serve in many industries e.g. as biochemical building blocks for bioplastics or biofuels, or as antioxidants, flavor agents or food preservatives. In nature, lignin is degraded by microorganisms, which results in the release of homocyclic aromatic compounds. Homocyclic aromatic compounds can also be linked to polysaccharides, tannins and even found freely in plant biomass. As these compounds are often toxic to microbes already at low concentrations, they need to be degraded or converted to less toxic forms. Prior to ring cleavage, the plant- and lignin-derived aromatic compounds are converted to seven central ring-fission intermediates, i.e. catechol, protocatechuic acid, hydroxyquinol, hydroquinone, gentisic acid, gallic acid and pyrogallol through complex aromatic metabolic pathways and used as energy source in the tricarboxylic acid cycle. Over the decades, bacterial aromatic metabolism has been described in great detail. However, the studies on fungal aromatic pathways are scattered over different pathways and species, complicating a comprehensive view of fungal aromatic metabolism. In this review, we depicted the similarities and differences of the reported aromatic metabolic pathways in fungi and bacteria. Although both microorganisms share the main conversion routes, many alternative pathways are observed in fungi. Understanding the microbial aromatic metabolic pathways could lead to metabolic engineering for strain improvement and promote valorization of lignin and related aromatic compounds.Peer reviewe

Half-AUC for the evaluation of sensitive or specific classifiers

This paper describes a simple, non-parametric variant of area under the receiver operating characteristic (ROC) curve (AUC), which we call half-AUC (HAUC). By measuring AUC in two halves: first when the true positive rate (TPR) is greater than the true negative rate (TNR) and then when TPR is less than TNR, we obtain a measure of a classifier's overall sensitivity (HAUC(Se)) and specificity (HAUC(Sp)) respectively. We show that these HAUC measures can be interpreted as the probability of correct ranking under the constraint that one class must have a higher detection rate than the other. We then go on to describe application domains where this constraint is appropriate and hence where HAUC may be superior to AUC. We show examples where HAUC discriminates ROC curves both when one curve dominates another and when the curves cross, but have an equivalent AUC. (C) 2013 Elsevier B.V. All rights reserved

Finite covers of random 3-manifolds

A 3-manifold is Haken if it contains a topologically essential surface. The Virtual Haken Conjecture posits that every irreducible 3-manifold with infinite fundamental group has a finite cover which is Haken. In this paper, we study random 3-manifolds and their finite covers in an attempt to shed light on this difficult question. In particular, we consider random Heegaard splittings by gluing two handlebodies by the result of a random walk in the mapping class group of a surface. For this model of random 3-manifold, we are able to compute the probabilities that the resulting manifolds have finite covers of particular kinds. Our results contrast with the analogous probabilities for groups coming from random balanced presentations, giving quantitative theorems to the effect that 3-manifold groups have many more finite quotients than random groups. The next natural question is whether these covers have positive betti number. For abelian covers of a fixed type over 3-manifolds of Heegaard genus 2, we show that the probability of positive betti number is 0. In fact, many of these questions boil down to questions about the mapping class group. We are lead to consider the action of mapping class group of a surface S on the set of quotients pi_1(S) -> Q. If Q is a simple group, we show that if the genus of S is large, then this action is very mixing. In particular, the action factors through the alternating group of each orbit. This is analogous to Goldman's theorem that the action of the mapping class group on the SU(2) character variety is ergodic.Comment: 60 pages; v2: minor changes. v3: minor changes; final versio

BET Inhibition-Induced GSK3&#946; Feedback Enhances Lymphoma Vulnerability to PI3K Inhibitors

The phosphatidylinositol 3 kinase (PI3K)-glycogen synthase kinase \u3b2 (GSK3\u3b2) axis plays a central role in MYC-driven lymphomagenesis, and MYC targeting with bromodomain and extraterminal protein family inhibitors (BETi) is a promising treatment strategy in lymphoma. In a high-throughput combinatorial drug screening experiment, BETi enhance the antiproliferative effects of PI3K inhibitors in a panel of diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma cell lines. BETi or MYC silencing upregulates several PI3K pathway genes and induces GSK3\u3b2 S9 inhibitory phosphorylation, resulting in increased \u3b2-catenin protein abundance. Furthermore, BETi or MYC silencing increases GSK3\u3b2 S9 phosphorylation levels and \u3b2-catenin protein abundance through downregulating the E2 ubiquitin conjugating enzymes UBE2C and UBE2T. In a mouse xenograft DLBCL model, BETi decrease MYC, UBE2C, and UBE2T and increase phospho-GSK3\u3b2 S9 levels, enhancing the anti-proliferative effect of PI3K inhibitors. Our study reveals prosurvival feedbacks induced by BETi involving GSK3\u3b2 regulation, providing a mechanistic rationale for combination strategies. In this study, Derenzini et al. demonstrate that BET inhibitors enhance lymphoma vulnerability to PI3K inhibitors by inducing GSK3\u3b2 feedback in a MYC-dependent manner and by downregulating E2-ubiquitin conjugating enzymes, which further enhance the feedback. These data provide the rationale for combining BET and PI3K inhibitors in lymphoma therapy