240 research outputs found

    When the Cut Condition is Enough: A Complete Characterization for Multiflow Problems in Series-Parallel Networks

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    Let G=(V,E)G=(V,E) be a supply graph and H=(V,F)H=(V,F) a demand graph defined on the same set of vertices. An assignment of capacities to the edges of GG and demands to the edges of HH is said to satisfy the \emph{cut condition} if for any cut in the graph, the total demand crossing the cut is no more than the total capacity crossing it. The pair (G,H)(G,H) is called \emph{cut-sufficient} if for any assignment of capacities and demands that satisfy the cut condition, there is a multiflow routing the demands defined on HH within the network with capacities defined on GG. We prove a previous conjecture, which states that when the supply graph GG is series-parallel, the pair (G,H)(G,H) is cut-sufficient if and only if (G,H)(G,H) does not contain an \emph{odd spindle} as a minor; that is, if it is impossible to contract edges of GG and delete edges of GG and HH so that GG becomes the complete bipartite graph K2,pK_{2,p}, with p≥3p\geq 3 odd, and HH is composed of a cycle connecting the pp vertices of degree 2, and an edge connecting the two vertices of degree pp. We further prove that if the instance is \emph{Eulerian} --- that is, the demands and capacities are integers and the total of demands and capacities incident to each vertex is even --- then the multiflow problem has an integral solution. We provide a polynomial-time algorithm to find an integral solution in this case. In order to prove these results, we formulate properties of tight cuts (cuts for which the cut condition inequality is tight) in cut-sufficient pairs. We believe these properties might be useful in extending our results to planar graphs.Comment: An extended abstract of this paper will be published at the 44th Symposium on Theory of Computing (STOC 2012

    Building a Sentiment Corpus of Tweets in Brazilian Portuguese

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    The large amount of data available in social media, forums and websites motivates researches in several areas of Natural Language Processing, such as sentiment analysis. The popularity of the area due to its subjective and semantic characteristics motivates research on novel methods and approaches for classification. Hence, there is a high demand for datasets on different domains and different languages. This paper introduces TweetSentBR, a sentiment corpora for Brazilian Portuguese manually annotated with 15.000 sentences on TV show domain. The sentences were labeled in three classes (positive, neutral and negative) by seven annotators, following literature guidelines for ensuring reliability on the annotation. We also ran baseline experiments on polarity classification using three machine learning methods, reaching 80.99% on F-Measure and 82.06% on accuracy in binary classification, and 59.85% F-Measure and 64.62% on accuracy on three point classification.Comment: Accepted for publication in 11th International Conference on Language Resources and Evaluation (LREC 2018

    Mitochondrial ATP Synthase is a Target of Oxidative Stress in Neurodegenerative Diseases

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    The mitochondrial ATP synthase is responsible for the production of cellular ATP, and it does so by harnessing the membrane potential of the mitochondria that is produced by the sequential oxidation of select cellular metabolites. Since the structural features of ATP synthase were first resolved nearly three decades ago, significant progress has been made in understanding its role in health and disease. Mitochondrial dysfunction is common to neurodegeneration, with elevated oxidative stress a hallmark of this dysfunction. The patterns of this oxidative stress, including molecular targets and the form of oxidative modification, can vary widely. In this mini review we discuss the oxidative modifications of ATP synthase that have been observed in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Oxidative modifications of ATP synthase in Alzheimer’s disease are well-documented, and there is a growing body of knowledge on the subject in Parkinson’s disease. The consideration of ATP synthase as a pharmacological target in a variety of diseases underlines the importance of understanding these modifications, both as a potential target, and also as inhibitors of any pharmacological intervention

    Autophagy activation and enhanced mitophagy characterize the Purkinje cells of pcd mice prior to neuronal death

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    Purkinje cells are a class of specialized neurons in the cerebellum, and are among the most metabolically active of all neurons, as they receive immense synaptic stimulation, and provide the only efferent output from the cerebellum. Degeneration of Purkinje cells is a common feature of inherited ataxias in humans and mice. To understand Purkinje neuron degeneration, investigators have turned to naturally occurring Purkinje cell degeneration phenotypes in mice to identify key regulatory proteins and cellular pathways. The Purkinje cell degeneration (pcd) mouse is a recessive mutant characterized by complete and dramatic post-natal, cell autonomous Purkinje neuron degeneration and death. As the basis of Purkinje cell death in pcd is unresolved, and contradictory data has emerged for the role of autophagy in Purkinje cell degeneration, we studied the mechanism of Purkinje cell death in pcd mice. BAX null status did not suppress Purkinje neuron death in pcd mice, indicating that classic apoptosis is not responsible for Purkinje cell loss. Interestingly, LC3 Western blot analysis and GFP-LC3 immunostaining of degenerating pcd cerebellum revealed activation of the autophagy pathway. Ultrastructural studies confirmed increased autophagy pathway activity in Purkinje cells, and yielded evidence for mitophagy, in agreement with LC3 immunoblotting of cerebellar fractions. As p62 levels were decreased in pcd cerebellum, our findings suggest that pcd Purkinje cell neurons can execute effective autophagy. However, our results support a role for dysregulated autophagy activation in pcd, and suggest that increased or aberrant mitophagy contributes to the Purkinje cell degeneration in pcd mice

    ATP synthase and Alzheimer's disease: putting a spin on the mitochondrial hypothesis

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    It is estimated that over 44 million people across the globe have dementia, and half of these cases are believed to be Alzheimer's disease (AD). As the proportion of the global population which is over the age 60 increases so will the number of individuals living with AD. This will result in ever-increasing demands on healthcare systems and the economy. AD can be either sporadic or familial, but both present with similar pathobiology and symptoms. Three prominent theories about the cause of AD are the amyloid, tau and mitochondrial hypotheses. The mitochondrial hypothesis focuses on mitochondrial dysfunction in AD, however little attention has been given to the potential dysfunction of the mitochondrial ATP synthase in AD. ATP synthase is a proton pump which harnesses the chemical potential energy of the proton gradient across the inner mitochondrial membrane (IMM), generated by the electron transport chain (ETC), in order to produce the cellular energy currency ATP. This review presents the evidence accumulated so far that demonstrates dysfunction of ATP synthase in AD, before highlighting two potential pharmacological interventions which may modulate ATP synthase

    Limited Viral Spread and Rapid Immune Response in Lymph Nodes of Macaques Inoculated with Attenuated Simian Immunodeficiency Virus

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    AbstractA comparative study was undertaken to characterize the very early events that distinguish attenuated and pathogenic simian immunodeficiency virus (SIV) infections. Three rhesus macaques were inoculated with the attenuated SIVmac 251 Δnef virus, and three others with a virus of intermediate phenotype, SIVmac 239 nef stop. They were compared to four macaques inoculated with the pathogenic SIVmac 251 isolate. Lymph nodes (LN) taken between 7 days and 2 months postinoculation were analyzed for SIV expression byin situhybridization. During acute infection, SIV 251 Δnef infected 1 to 1.5 log10fewer cells in LN tissue than the pathogenic SIV 251 isolate. The reduction was more marked in the blood, as SIV 251 Δnef infected 2 to 3 log10fewer PBMC than the isolate and did not yield detectable antigenemia. Morphometric measurements showed that the development of germinal centers (GC) was more rapid in the Δnef infection, which led to a more efficient trapping of viral particles, and could account for antigenemia clearance. The SIV 239 nef stop clone reverted to a nef+genotype at Week 2, but induced a lower viral burden than a directly pathogenic virus. The kinetics of GC development was rapid, indicating that SIV 239 nef stop induced an immune response similar to that seen in attenuated infection. This study provides evidence that attenuated SIV elicits a more rapid immune response than pathogenic SIV and suggests that an early immunosuppressive episode may facilitate the dissemination of pathogenic SIV

    A Common Anaesthetic, MS-222, Alters Measurements Made Using High-Resolution Respirometry in the Three-Spined Stickleback (Gasterosteus aculeatus)

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    Submersion in the anaesthetic MS-222 is a well-established and effective method used during the euthanasia of fish, but the consequences of treatment with this anaesthetic for mitochondrial respiration are yet to be established. This is important to evaluate, as an increasing amount of research is conducting high-resolution respirometry to measure respiration across multiple species of fish, including looking at thermal sensitivity and mitochondrial responses to the warmer temperatures faced with climate change. Analysis often occurs after euthanasia with MS-222 without knowledge of how MS-222 itself affects any measured parameters of mitochondrial respiration, leaving potential for a misinterpretation of results. Here, high-resolution respirometry was conducted to explore how MS-222 affects oxidative phosphorylation in the brain and skeletal muscle of the three-spined stickleback, Gasterosteus aculeatus, which is a model species in evolutionary ecology. In the brain, differences in respiration were observed between three-spined sticklebacks euthanised with MS-222 and those where no anaesthetic was implemented. No differences between treatments were observed in the skeletal muscle, although variation between individuals was high and oxygen flux was lower than in the brain. Overall, this study highlights the need for a consistent method of euthanasia when conducting high-resolution respirometry in fish, as MS-222 may alter measures of oxidative phosphorylation
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