42 research outputs found
Permutation Pattern matching in (213, 231)-avoiding permutations
No full textInternational audienceGiven permutations σ of size k and π of size n with k < n, the permutation pattern matching problem is to decide whether σ occurs in π as an order-isomorphic subsequence. We give a linear-time algorithm in case both π and σ avoid the two size-3 permutations 213 and 231. For the special case where only σ avoids 213 and 231, we present a O(max(kn², n² log log n)-time algorithm. We extend our research to bivincular patterns that avoid 213 and 231 and present a O(kn^4)-time algorithm. Finally we look at the related problem of the longest subsequence which avoids 213 and 231
Pattern Matching for Separable Permutations
No full textInternational audienceGiven a permutation π (called the text) of size n and another permutation σ (called the pattern) of size k, the NP-complete permutation pattern matching problem asks whether σ occurs in π as an order-isomorphic subsequence. In this paper, we focus on separable permutations (those permutations that avoid both 2413 and 3142, or, equivalently, that admit a separating tree). The main contributions presented in this paper are as follows.We simplify the algorithm of Ibarra (Finding pattern matchings for permutations, Information Processing Letters 61 (1997), no. 6) to detect an occurrence of a separable permutation in a permutation and show how to reduce the space complexity from O(n3k) to O(n3logk) .In case both the text and the pattern are separable permutations, we give a more practicable O(n2k) time and O(nk) space algorithm. Furthermore, we show how to use this approach to decide in O(nk3ℓ2) time whether a separable permutation of size n is a disjoint union of two given permutations of size k and ℓ .Given a permutation of size n and a separable permutation of size k, we propose an O(n6k) time and O(n4log k) space algorithm to compute the largest common separable permutation that occurs in the two input permutations. This improves upon the existing O(n8) time algorithm by Rossin and Bouvel (The longest common pattern problem for two permutations, Pure Mathematics and Applications 17 (2006)).Finally, we give a O(n6k) time and space algorithm to detect an occurrence of a bivincular separable permutation in a permutation. (Bivincular patterns generalize classical permutations by requiring that positions and values involved in an occurrence may be forced to be adjacent)
Recherche de motif dans les permutations
No full textThis thesis focuses on permutation pattern matching problem, which askswhether a pattern occurs in a text where both the pattern and text are permutations.In other words, we seek to determine whether there exist elements ofthe text such that they are sorted and appear in the same order as the elementsof the pattern. The problem is NP-complete. This thesis examines particularcases of the problem that are polynomial-time solvable.For this purpose, we study the problem by giving constraints on the permutationstext and/or pattern. In particular, the cases in which the text and/orpattern are permutations in which the patterns 2413 and 3142 do not occur(also known as separable permutations) and in which the text and/or patternare permutations in which the patterns 213 and 231 do not occur (also known aswedge permutations) are also considered. Some problems related to the patternmatching and the permutation pattern matching with bivincular pattern arealso studied.Cette thèse s'intéresse au problème de la recherche de motif dans les permutations, qui a pour objectif de savoir si un motif apparaît dans un texte, en prenant en compte que le motif et le texte sont des permutations. C'est-à-dire s'il existe des éléments du texte tel que ces éléments sont triés de la même manière et apparaissent dans le même ordre que les éléments du motif. Ce problème est NP complet. Cette thèse expose des cas particuliers de ce problème qui sont solvable en temps polynomial.Pour cela nous étudions le problème en donnant des contraintes sur le texte et/ou le motif. En particulier, le cas où le texte et/ou le motif sont des permutations qui ne contiennent pas les motifs 2413 et 3142 (appelé permutation séparable) et le cas où le texte et/ou le motif sont des permutations qui ne contiennent pas les motifs 213 et 231 sont considérés. Des problèmes dérivés de la recherche de motif et le problème de la recherche de motif bivinculaire sont aussi étudiés
Recherche de motif dans les permutations
No full textThis thesis focuses on permutation pattern matching problem, which askswhether a pattern occurs in a text where both the pattern and text are permutations.In other words, we seek to determine whether there exist elements ofthe text such that they are sorted and appear in the same order as the elementsof the pattern. The problem is NP-complete. This thesis examines particularcases of the problem that are polynomial-time solvable.For this purpose, we study the problem by giving constraints on the permutationstext and/or pattern. In particular, the cases in which the text and/orpattern are permutations in which the patterns 2413 and 3142 do not occur(also known as separable permutations) and in which the text and/or patternare permutations in which the patterns 213 and 231 do not occur (also known aswedge permutations) are also considered. Some problems related to the patternmatching and the permutation pattern matching with bivincular pattern arealso studied.Cette thèse s'intéresse au problème de la recherche de motif dans les permutations, qui a pour objectif de savoir si un motif apparaît dans un texte, en prenant en compte que le motif et le texte sont des permutations. C'est-à-dire s'il existe des éléments du texte tel que ces éléments sont triés de la même manière et apparaissent dans le même ordre que les éléments du motif. Ce problème est NP complet. Cette thèse expose des cas particuliers de ce problème qui sont solvable en temps polynomial.Pour cela nous étudions le problème en donnant des contraintes sur le texte et/ou le motif. En particulier, le cas où le texte et/ou le motif sont des permutations qui ne contiennent pas les motifs 2413 et 3142 (appelé permutation séparable) et le cas où le texte et/ou le motif sont des permutations qui ne contiennent pas les motifs 213 et 231 sont considérés. Des problèmes dérivés de la recherche de motif et le problème de la recherche de motif bivinculaire sont aussi étudiés
Green Growth or Degrowth: Two Opposing Paths to Environmental Sustainability
No full textIn the wake of worsening climate change, environmental sustainability is more important than ever if we wish to mitigate disaster and preserve our way of life. This paper will compare two methods of achieving environmental sustainability. The first is green growth, which attempts to replace non-renewable natural resources with renewable ones, and increase efficiency, while continuing to let the economy grow as usual. The second is degrowth, which advocates for a radical restructuring of society, and accepts a decrease in economic growth as a necessary consequence. The comparison will show that green growth is not good enough, because the mass consumption that results from endless economic growth is partly what drove greenhouse gas levels to what they are today. A drastic change in consumption patterns is needed to deal with climate change, and degrowth seems more likely to achieve this.Peer reviewe
The severity of SARS‐CoV‐2 infection in K18‐hACE2 mice is attenuated by a novel steroid‐derivative in a gender‐specific manner
No full textBACKGROUND AND PURPOSE: COVID-19 infections caused by SARS-CoV-2 disseminated through human-to-human transmission can evoke severe inflammation. Treatments to reduce the SARS-CoV-2-associated inflammation are needed and are the focus of much research. In this study, we investigated the effect of N-ethyl-N\u27-[(3β,5α)-17-oxoandrostan-3-yl] urea (NEOU), a novel 17α-ketosteroid derivative, on the severity of COVID-19 infections. EXPERIMENTAL APPROACH: Studies were conducted in SARS-CoV-2-infected K18-hACE2 mice. KEY RESULTS: SARS-CoV-2-infected K18-hACE2 mice developed severe inflammatory crises and immune responses along with up-regulation of genes in associated signalling pathways in male more than female mice. Notably, SARS-CoV-2 infection down-regulated genes encoding drug metabolizing cytochrome P450 enzymes in male but not female mice. Treatment with NEOU (1 mg·kg ·day ) 24 or 72 h post-viral infection alleviated lung injury by decreasing expression of genes encoding inflammatory cytokines and chemokines while increasing expression of genes encoding immunoglobins. In situ hybridization using RNA scope™ probes and immunohistochemical assays revealed that NEOU increased resident CD169 immunoregulatory macrophages and IBA-1 immunoreactive macrophage-dendritic cells within alveolar spaces in the lungs of infected mice. Consequentially, NEOU reduced morbidity more prominently in male than female mice. However, NEOU increased median survival time and accelerated recovery from infection by 6 days in both males and females. CONCLUSIONS AND IMPLICATIONS: These findings demonstrate that SARS-CoV-2 exhibits gender bias by differentially regulating genes encoding inflammatory cytokines, immunogenic factors and drug-metabolizing enzymes, in male versus female mice. Most importantly, we identified a novel 17α-ketosteroid that reduces the severity of COVID-19 infection and could be beneficial for reducing impact of COVID-19
Deciphering full omics of pituitary tumors : classification, diagnostic and pronostic
No full textLes adénomes hypophysaires sont des tumeurs bénignes développées aux dépends de l'hypophyse. Elles sont fréquentes (5% de la population). Leur phénotype varie selon : - l'agressivité tumorale, c'est-à-dire la taille, la vitesse de croissance, l'invasion et la compression des structures adjacentes - la sécrétion hormonale, c'est-à-dire le type de sécrétion (prolactine, hormone croissance, corticotropine, thyréostimuline), et son intensité. La classification actuelle de ces tumeurs repose essentiellement sur l'histologie (classification de l'organisation mondiale de la santé (OMS) 2017). Cette classification s'appuie sur le profil d'expression de facteurs de transcription spécifiques de chaque lignage ante-hypophysaire : lignage PIT1 (adénomes lacto- somato- et thyréotropes), lignage TPIT (adénomes corticotropes) et lignage SF1 (adénomes gonadotropes). Cette classification reflète mal l'agressivité tumorale. L'objectif essentiel de cette thèse était de fournir la première classification génomique des adénomes hypophysaires. Pour cela, une caractérisation clinique, histologique et génomique de 134 PitNETs de tous les sous-types a été effectué, combinant mutations (séquençage d'exome), transcriptome (séquençage des ARNm), miRnome (séquençage des microARN), anomalies chromosomiques (puces SNP) et méthylome de l'ADN (puces méthylome). Une analyse indépendante de chaque omique a été effectuée puis une analyse intégrée combinée. L'analyse des profils chromosomiques ont décrit trois groupes : profil avec perte étendue sur le génome, profil avec peu d'altérations et profil avec des gains étendus sur le génome. Ces altérations étaient liées au type sécrétoire (moins d'anomalies dans les tumeurs gonadotropes), mais indépendantes de l'agressivité. L'analyse épigénétique (miRnome et méthylome ) discriminait nettement le lignage PIT1 des autres lignages, avec principalement un profil d'hypométhylation globale du génome, et un profil miRNA spécifique. L'hypométhylation était corrélée à l'instabilité chromosomique et à la surexpression d'éléments transposables. L'analyse transcriptome a retrouvé en classification non supervisée six groupes, associés au sous-type histologique et à la sécrétion. On retrouvait globalement les même conclusions que l'OMS, avec des précisions supplémentaires : - le type « null-cell » était fusionné avec les gonadotropes - les corticotropes silencieux formaient un groupe différent des corticotropes sécrétants, en rapport avec une transdifférenciation gonadique. - au sein des adénomes corticotropes sécrétants, les mutés USP8 formaient un sous-groupe à part. - les thyréotropes et les plurihormonaux-Pit1 étaient classés ensemble, avec la plupart des somatotropes à granules éparses. - les adénomes mixtes GH-PRL étaient dans le même groupe que les adénomes somatotropes, et distincts des adénomes lactotropes. Au sein des adénomes somatotropes, les mutés GNAS formaient un sous-groupe à part. Dans le cadre d'une analyse intégrée combinant toutes ces approches d'omics, les adénomes hypophysaires ont été projetés dans une représentation multidimensionnelle. Dans cette représentation moléculaire non supervisée, la classification reprenant les 6 groupes du transcriptome et le statut mutationnel GNAS et USP8 forme des groupes plus homogènes et mieux séparés que la classification histologique OMS 2017. Sur le plan clinique, l'agressivité des tumeurs apparaissait comme un déterminant moins fort de la classification moléculaire que le lignage hypophysaire. Au sein des adénomes corticotropes, les adénomes avec sécrétion franche et sans mutation USP8 formaient un sous-groupe plus agressif tant cliniquement qu'en terme de transcriptome (signature de prolifération). Cette thèse dévoile des aspects nouveaux de la biologie des adénomes hypophysaires.Ces données importantes devraient ouvrir la voie à de nouveaux axes de recherches.Pituitary adenomas are benign tumors developed from the pituitary gland. They are common (5% of the population). Their phenotype varies according to: - tumor aggressiveness, ie size, rate of growth, invasion and compression of adjacent structures - the hormonal secretion, ie the type of secretion (prolactin, growth hormone, corticotropin, thyreostimulin), and its intensity. The current classification of these tumors is based primarily on histology (World Health Organization (WHO) classification 2017). This classification is based on the expression profile of specific transcription factors of each ante-pituitary lineage: PIT1 lineage for lacto- somato- thyrotroph adenomas, TPIT lineage for corticotroph adenomas and SF1 lineage for gonadotroph adenomas. This classification does not reflect the aggressiveness of the tumor. The main objective of this thesis was to provide the first genomic classification of pituitary adenomas. For this, a clinical, histological and genomic characterization of 134 PitNETs of all subtypes was performed, combining mutations (exome sequencing), transcriptome (mRNA sequencing), miRnome (microRNA sequencing), chromosomal abnormalities (SNP microarrays),and DNA methylome (methylome chips). An independent analysis of each omic was carried out then an integrated analysis combining all the methods. Analysis of the chromosome profiles described three groups: one with extensive loss on the genome, one with few alterations and one with extensive gains on the genome. These alterations were associated to the secretory type (less anomaly in gonadotropic tumors), but independent of aggressiveness. Epigenetic analysis (miRnome and methylome) clearly discriminated the PIT1 lineage from other lineages, mainly with a global genome hypomethylation profile, and a specific miRNA profile. Hypomethylation was correlated with chromosomal instability and overexpression of transposable elements. The transcriptome analysis found in unsupervised classification six groups, associated with histological subtype and secretion. The same conclusions were found overall as WHO, with additional details: - the "null-cell" type was merged with gonadotrophs -silent corticotrophs formed a different group from secreting corticotrophs, related to a gonadal transdifferentiation. Within the secretory corticotropic adenomas, the USP8 mutants formed a separate subgroup. -the thyrotropic and the plurihormonal PIT1 were classified together with most of the sparsely granulated somatotrophs. -the mixed GH-PRL adenomas were in the same group as the somatotroph adenomas, and distinct from the lactotroph adenomas. Within the somatotroph adenomas, the GNAS mutated formed a separate subgroup. As part of an integrated analysis combining all these omics approaches, pituitary adenomas were projected into a multidimensional representation. In this unsupervised molecular representation, the classification based on the six transcriptome groups and the mutation status GNAS and USP8 forme more homogeneous and better separated groups than the histological classification OMS 2017. Clinically, tumor aggressiveness appeared to be a weaker determinant of the molecular classification than the pituitary lineage. Within corticotropic adenomas, USP8-wild type adenomas formed a more aggressive subgroup both clinically and at the transcriptome level (proliferative signature). This thesis unveils new aspects of the biology of pituitary adenomas. It is also the first unsupervised molecular classification of pituitary adenomas. These important data should pave the way for new lines of research
How to promote democracy in the ASEAN region The Cambodian example
No full text'Cambodia is a useful example in some ways for the promotion of democracy in ASEAN; in other ways it is not. Over the first quarter of this century, Cambodia suffered greatly, perhaps more than virtually any country in the world. War, genocide, political oppression, and international isolation all contributed to one of the bloodiest, most turbulent periods that any country has ever endured. Yet today, as Thomas Hammerburg, the UN Secretary General's Special Representative for Human Rights in Cambodia wrote in 1996: 'Cambodian society has made truly remarkable progress since 1993. Within three years after the formation of the Government, Cambodia has become one of the freest countries in the region.' What is responsible for this remarkable transformation? The short answer is a great deal of effort, by Cambodians and by the international community. But I would like also to emphasize that the democracy that emerged in Cambodia is still very fragile. Many people are working to ensure its survival, but that is not an assured outcome. The author will tell about some of the obstacles, and some of the successes, in these efforts.' (author's abstract)Der vorliegende Beitrag untersucht die Moeglichkeiten der Demokratisierung in der ASEAN-Region am Beispiel Kambodschas. Kambodscha stellt in vielerlei Hinsicht ein nuetzliches Beispiel fuer die Demokratisierung dieser Region dar, in anderen Bereichen ist es nicht so aussagekraeftig. Seit 1970 hat Kambodscha, vielleicht mehr als jedes andere Land auf der Welt, gelitten. Krieg, Voelkermord, politische Unterdrueckung und internationale Isolierung haben zu einem der blutigsten und turbulentesten Zeitabschnitte beigetragen. Doch momentan, wie Thomas Hammerburg, der Sonderrepraesentant fuer Menschenrechte des UNO-Generalsekretaers 1996 geschrieben hat, macht Kambodscha seit 1993 beachtliche Fortschritte. Innerhalb von drei Jahren nach der Regierungsbildung wurde Kambodscha eines der freisten Laender der Region. Was ist fuer diese beachtliche Transformation verantwortlich? Zunaechst sind die grossen Anstrengungen der Kambodschaner und der internationalen Gemeinschaft zu nennen. Es muss allerdings festgestellt werden, dass die Demokratie, die in Kambodscha entstanden ist, noch sehr zerbrechlich ist. Viele Menschen arbeiten daran, deren Ueberleben zu sichern, aber es nicht sicher, ob dies gelingt. Der Autor stellt einige Hindernisse und Erfolge in diesem Zusammenhang vor. (ICDUebers)German title: Wie kann Demokratie in der ASEAN-Region gefoerdert werden?: das Beispiel KambodschaAvailable from http://www.uni-duisburg.de/Institute/OAWISS/download/doc/discuss7.pdf / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman
Identification of glucocorticoid-related molecular signature by whole blood methylome analysis
No full textObjective: Cushing's syndrome represents a state of excessive glucocorticoids related to glucocorticoid treatments or to endogenous hypercortisolism. Cushing's syndrome is associated with high morbidity, with significant inter-individual variability. Likewise, adrenal insufficiency is a life-threatening condition of cortisol deprivation. Currently, hormone assays contribute to identify Cushing's syndrome or adrenal ins ufficiency. However, no biomarker directly quantifies the biological glucocorticoid action. The aim of this study was to identify such markers. Design: We evaluated whole blood DNA methylome in 94 samples obtained from patients with different glucocorticoid states (Cushing's syndrome, eucortisolism, adrenal insufficiency). We used an independent cohort of 91 samples for validation. Methods: Leukocyte DNA was obtained from whole blood samples. Methylome was determined using the Illumina methylation chip array (~850 000 CpG sites). Both unsupervised (principal component analysis) and supervised (Limma) methods were used to explore methylome profiles. A Lasso -penalized regression was used to select optimal discriminating features. Results: Whole blood methylation profile was able to discriminate sample s by their glucocorticoid status: glucocorticoid excess was associated with DNA hypomethylation, recovering within months after Cushing's syndrome correction. In Cushing's syndrome, an enrichment in hypomethylated CpG sites was observed in the region of FKBP5 gene locus. A methylation predictor of glucocorticoid excess was built on a training cohort and validated on two independent cohorts. Potential CpG sites associated with the risk for speci fic complications, such as glucocorticoid-related hypertension or osteoporosis, were identified, needing now to be confirmed on independent cohorts. Conclusions: Whole blood DNA methylome is dynamically impacted by glucocorticoids. This biomarker could contribute to better assessment of glucocorticoid action beyond hormone assays
Heteroresistance to meropenem in carbapenem-susceptible Acinetobacter baumannii
No full textThe characteristics of carbapenem heteroresistance were studied in 14 apparently carbapenem-susceptible Acinetobacter baumannii isolates. The MICs for carbapenems were determined, and the isolates were genotyped by pulsed-field gel electrophoresis (PFGE) and sequence typing (ST). Population analysis, testing of the stability of the heteroresistant subpopulations, and time-killing assays were performed. The agar dilution MICs of both imipenem and meropenem for the native isolates ranged from 0.25 to 4 mg/liter. The isolates belonged to nine PFGE types and exhibited seven ST allelic profiles. Population analysis revealed subpopulations that grew in the presence of imipenem at concentrations of up to 8 mg/liter and meropenem at concentrations of up to 32 mg/liter. The meropenem-heteroresistant subpopulations of 11 isolates exhibited stable resistance with MICs that ranged from 16 to >32 mg/liter; their PFGE profiles were identical to those of the native isolates. Time-kill assays with meropenem revealed less pronounced killing for 10 isolates. These findings indicate that meropenem pressure can produce meropenem-heteroresistant subpopulations that might subsequently select for highly resistant strains. Copyright © 2009, American Society for Microbiology. All Rights Reserved
