Tree decomposition and parameterized algorithms for RNA structure-sequence alignment including tertiary interactions and pseudoknots

We present a general setting for structure-sequence comparison in a large class of RNA structures that unifies and generalizes a number of recent works on specific families on structures. Our approach is based on tree decomposition of structures and gives rises to a general parameterized algorithm, where the exponential part of the complexity depends on the family of structures. For each of the previously studied families, our algorithm has the same complexity as the specific algorithm that had been given before.Comment: (2012

The permutation-path coloring problem on trees

AbstractIn this paper we first show that the permutation-path coloring problem is NP-hard even for very restrictive instances like involutions, which are permutations that contain only cycles of length at most two, on both binary trees and on trees having only two vertices with degree greater than two, and for circular permutations, which are permutations that contain exactly one cycle, on trees with maximum degree greater than or equal to 4. We calculate a lower bound on the average complexity of the permutation-path coloring problem on arbitrary networks. Then we give combinatorial and asymptotic results for the permutation-path coloring problem on linear networks in order to show that the average number of colors needed to color any permutation on a linear network on n vertices is n/4+o(n). We extend these results and obtain an upper bound on the average complexity of the permutation-path coloring problem on arbitrary trees, obtaining exact results in the case of generalized star trees. Finally we explain how to extend these results for the involutions-path coloring problem on arbitrary trees

Endovascular Treatment of Anterior Circulation Cerebral Aneurysms by Using Guglielmi Detachable Coils: A 10-Year Single-Center Experience with Special Emphasis on the Use of Three-Dimensional GDC

Purpose:: To analyze the immediate, long-term angiographic and clinical results of endovascular treatment of anterior circulation aneurysms with special regard to the use of three-dimensional Guglielmi detachable coils (3D-GDC). Patients and Methods:: Between 1993 and 2003, 116 patients with 116 anterior circulation aneurysms were treated. 88 patients (75.9%) underwent embolization due to high surgical risk. To analyze the use of 3D-GDC, patients treated before (group 1) and after (group 2) implementation of 3D-GDC in 1999 were compared. Mean duration of angiographic follow-up was 13.9 months. Clinical follow-up was set at hospital discharge and using a questionnaire for long-term follow-up (mean 46.8 months). Results:: Overall, at initial intervention, complete occlusion was achieved in 65 aneurysms (56.0%), neck remnant in 42 (36.2%), and incomplete occlusion in nine (7.8%). Procedure-related permanent morbidity was 4.3% and mortality 2.6%. Recanalization rate at radiologic follow-up was 16.7%. Occlusion success at initial treatment correlated with aneurysm neck size (p = 0.001). Clinical outcome at hospital discharge was dependent on Hunt & Hess grade at presentation (p = 0.01). Subgroup analysis revealed that the use of 3D-GDC produced a higher initial obliteration rate compared to standard coils, but did not reach statistical significance (p = 0.059). Neither aneurysm neck size nor aneurysm dome size nor the use of 3D-GDC significantly influenced recanalization rate. Conclusion:: GDC technology is effective and safe, particularly in case of patients with high surgical risk. Aneurysm neck size was predictive of occlusion rate and Hunt & Hess grade of clinical outcome. Introduction of 3D-GDC probably improved occlusion rate, but did not significantly influence recanalization rat

Algorithmique de l'alignement structure-séquence d'ARN (une approche générale et paramétrée)

L'alignement de macromolécules biologiques comme les protéines, l'ADN ou encore l'ARN est une problématique biologique et bio-informatique qui a pour but de révéler une partie des mystères du fonctionnement des cellules, constituants des êtres vivants. Les ARN non-codant sont des macromolécules intervenant dans le métabolisme de tout être vivant et les deux problématiques majeurs les concernant sont: la prédiction de leur structure pour mieux comprendre leur fonctionnement et leur détection dans des bases de données ou des génomes. L'une des approches: l'alignement structure-séquence d'ARN, répond à ces deux problématiques. Le problème d'alignement structure-séquence consiste à aligner une structure connue d'un premier ARN avec la séquence d'un deuxième ARN.La structure est représentée sous la forme d'un graphe ou de façon équivalente sous la forme d'une séquence arc-annotées et la séquence représente la suite des nucléotides de l'ARN.Pour résoudre ce problème, nous cherchons à optimiser l'alignement selon une fonction de coût. C'est donc un problème d'optimisation, qui malheureusement se révèle NP-Difficile.En conséquence différents travaux définissent des classes d'instances réduites pour lesquelles ils proposent des algorithmes spécifiques mais à complexités polynomiales.Les travaux de ma thèse unifient et la généralisent les approches précédentes par la construction d'un algorithme à complexité paramétrée non spécifique à une classe d'instances. En utilisant cet algorithme, il est possible de résoudre le problème d'alignement structure-séquence pour toutes les instances possibles, et aussi efficacement que les précédentes approches sur leur domaine de résolution respectif. Cet algorithme utilise une technique empruntée à la théorie des graphes: la décomposition arborescente, c'est-à-dire qu'il transforme la structure donnée en une décomposition arborescente et c'est ensuite cette décomposition qui est alignée avec la séquence donnée. L'alignement entre une décomposition arborescente et une séquence se fait par programmation dynamique.Sa mise en place a nécessité une reformulation du problème ainsi qu'une modification importante de l'utilisation classique de la programmation dynamique pour les décompositions arborescentes. Au final, cela conduit à un algorithme paramétré dont le paramètre est entièrement lié à la décomposition arborescente. La construction des décompositions arborescentes pour lesquelles l'alignement s'effectuera plus le efficacement possible est malheureusement un problème lui aussi NP-Difficile. Néanmoins, nous avons créé une heuristique de construction de décompositions adaptée aux structures d'ARN.Nous avons alors défini des nouvelles classes de structures pour lesquelles notre algorithme (décomposition et alignement) possède une faible complexité. Ces classes incluent notamment toutes les autres classes précédemment définies et la complexité de notre algorithme est au moins aussi faible que celles des algorithmes spécifiques sur leurs classes de structures respectives. Ces classes de structures représentent la majorité des structures connues et contiennent de nombreux éléments importants jusqu'alors non pris en compte (tel que les motifs tertiaires d'ARN). Le problème de l'alignement structure-séquence tente de répondre aux problématiques de prédictions de structures et de recherche d'ARN. Néanmoins, la qualité des résultats obtenus par sa résolution dépendent de la fonction de coût utilisée. Durant ma thèse j'ai commencé la mise place de la construction par apprentissage d'une nouvelle fonction de coût, adaptée aux nouvelles classes de structures que nous avons défini. Enfin de par la nature de l'algorithme, le travail réalisé permet des améliorations non négligeables, en terme de qualité des résultats et de rapidité de calcul comme la recherche de solution sous-optimales ou l'utilisation de l'algorithme au sein d'heuristiques dérivées d'heuristiques classiques.The alignment of biological macromolecules such as proteins, DNA or RNA is a biological and bio-informatics problematic which aims to reveal some of the mysteries of how cells works. The non-coding RNA are involved in the metabolism of all living beings. The two major issues concerning them are: the prediction of their structure to better understand their function and their detection in databases or genomes. One approach, the structure-sequence alignment of RNA, addresses these two issues. The work done during my thesis provides some constructive elements on this problem and led me to call the graph algorithmic for its resolution. The alignment problem is to align a structure of a first RNA with the sequence of a second RNA. The structure on the first RNA is represented as a graph or equivalently as an arc-annotated sequence and the sequence represents the nucleotide sequence of the second RNA.To solve this problem, we aim to compute a minimal cost alignment, according to a given cost function. So, this is an optimization problem, which turns out to be NP-hard.Accordingly, different works define several reduced structure classes for which they propose specific algorithms but with polynomial complexity. The work of my thesis unifies and generalizes previous approaches by the construction of a unique (not class specific) parameterized algorithm. Using this algorithm, it is possible to solve the problem of structure-sequence alignment for all possible instances, and as effectively as previous approaches in their respective field of resolution.This algorithm uses a technique from graph theory: the tree decomposition, that is to say, it transforms the given structure into a tree-decomposition and the decomposition is then aligned with the sequence. The alignment between a tree-decomposition and a sequence is done by dynamic programming. Its implementation requires a reformulation of the problem as well as a substantial modifications to the conventional use of dynamic programming for tree decompositions. This leads to an algorithm whose parameter is entirely related to the tree-decomposition.The construction of tree decompositions for which the alignment is the most effective is unfortunately a NP-Hard problem. Nevertheless, we have developed a heuristic construction of decompositions adapted to RNA structures. We then defined new structure classes which extend existing ones without degrading the complexity of the alignment but which can represent the majority of known structures containing many important elements that had not be taken into account previously (such as RNA tertiary motifs).The sequence-structure alignment problem attempts to answer the problem of prediction of structures and RNA research. However, the quality of the results obtained by its resolution depends on the cost function. During my PhD I started to define new cost functions adapted to the new structure classes by a machine learning approach. Finally, the work allows significant improvements in terms of quality of results and computation. For example the approach directly allows the search for sub-optimal solutions or its use within heuristics derived from traditional heuristic methods.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Sums of residues on algebraic surfaces and application to coding theory

In this paper, we study residues of differential 2-forms on a smooth algebraic surface over an arbitrary field and give several statements about sums of residues. Afterwards, using these results we construct algebraic-geometric codes which are an extension to surfaces of the well-known differential codes on curves. We also study some properties of these codes and extend to them some known properties for codes on curves.Comment: 31 page

Endovascular and surgical treatment of spinal dural arteriovenous fistulas

Introduction: The aim of this retrospective study was to evaluate the clinical outcome of patients with spinal dural arteriovenous fistulas (SDAVFs) that were treated with surgery, catheter embolization, or surgery after incomplete embolization. Methods: The study included 21 consecutive patients with SDAVFs of the thoracic, lumbar, or sacral spine who were treated in our institution from 1994 to 2007. Thirteen patients were treated with catheter embolization alone. Four patients underwent hemilaminectomy and intradural interruption of the fistula. Four patients were treated by endovascular techniques followed by surgery. The clinical outcome was assessed using the modified Aminoff-Logue scale (ALS) for myelopathy and the modified Rankin scale (MRS) for general quality of life. Patient age ranged from 44 to 77years (mean 64.7years). Results: Surgical as well as endovascular treatment resulted in a significant improvement in ALS (−62.5% and −31.4%, respectively, p < 0.05) and a tendency toward improved MRS (−50% and −32%, respectively) scores. Patients that underwent surgery after endovascular treatment due to incomplete occlusion of the fistula showed only a tendency for improvement in the ALS score (−16.7%), whereas the MRS score was not affected. Conclusion: We conclude that both endovascular and surgical treatment of SDAVFs resulted in a good and lasting clinical outcome in the majority of cases. In specific situations, when a secondary neurosurgical approach was required after endovascular treatment to achieve complete occlusion of the SDAVF, the clinical outcome was rather poor. The best first line treatment modality for each individual patient should be determined by an interdisciplinary tea

Außergewöhnliche Manifestation eines Magenkarzinoms mit Meningeosis carcinomatosa und spinaler Metastase

Zusammenfassung: Hintergrund:: Eine Meningeosis carcinomatosa ist eine seltene Komplikation solider Tumoren, wie Mamma-, Bronchial- oder gastrointestinale Karzinome. Klinisch manifestiert sie sich mit einer äußerst variablen Symptomatik wie z. B. radikulären Schmerzen mit oder ohne neurologische Ausfälle sowie Kopfschmerzen bis hin zu halluzinatorischen Reizsymptomen. Fallbeschreibung:: Berichtet wird über den seltenen Fall eines 57-jährigen Patienten mit neurologischen Reiz- und Ausfallsymptomen, hervorgerufen durch eine Meningeosis carcinomatosa und eine spinale Metastase bei einem asymptomatischen Siegelringzellkarzinom des Magens. Trotz kombinierter Radiochemotherapie verstarb der Patient bereits 4 Wochen nach Entlassung aus dem Spital an einer Hirnblutung. Schlussfolgerung:: Die Prognose der Meningeosis carcinomatosa ist bis heute unabhängig vom Primärtumor mit einer mittleren Überlebenszeit von 3-4 Monaten sehr schlech

Restenosis after microsurgical non-patch carotid endarterectomy in 586 patients

Background: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic (>50%) and asymptomatic (>60%) carotid artery stenosis. Here we report the midterm results of a microsurgical non-patch technique and compare these findings to those in the literature. Methods: From 1998 to 2009 we treated 586 consecutive patients with CEA. CEA was performed, under general anesthesia, with a surgical microscope using a non-patch technique. Somatosensory evoked potential and transcranial Doppler were continuously monitored. Cross-clamping was performed under EEG burst suppression and adaptive blood pressure increase. Follow-up was performed by an independent neurologist. Mortality at 30 days and morbidity such as major and minor stroke, peripheral nerve palsy, hematoma and cardiac complications were recorded. The restenosis rate was assessed using duplex sonography 1 year after surgery. Results: A total of 439 (75%) patients had symptomatic and 147 (25%) asymptomatic stenosis; 49.7% of the stenoses were on the right-side. Major perioperative strokes occurred in five (0.9%) patients [n = 4 (0.9%) symptomatic; n = 1 (0.7%) asymptomatic patients]. Minor stroke was recorded in six (1%) patients [n = 4 (0.9%) symptomatic; n = 2 (1.3%) asymptomatic patients]. Two patients with symptomatic stenoses died within 1 month after surgery. Nine patients (1.5%) had reversible peripheral nerve palsies, and nine patients (1.5%) suffered a perioperative myocardial infarction. High-grade (>70%) restenosis at 1 year was observed in 19 (3.2%) patients [n = 12 (2.7%) symptomatic; n = 7 (4.7%) asymptomatic patients]. Conclusions: The midterm rate of restenosis was low when using a microscope-assisted non-patch endarterectomy technique. The 30-day morbidity and mortality rate was comparable or lower than those in recently published surgical serie

Restenosis after microsurgical non-patch carotid endarterectomy in 586 patients

Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic (>50%) and asymptomatic (>60%) carotid artery stenosis. Here we report the midterm results of a microsurgical non-patch technique and compare these findings to those in the literature

Pinealectomy affects bone mineral density and structure - an experimental study in sheep

<p>Abstract</p> <p>Background</p> <p>Osteoporosis and associated fractures are a major public health burden and there is great need for a large animal model. Melatonin, the hormone of the pineal gland, has been shown to influence bone metabolism. This study aims to evaluate whether absence of melatonin due to pinealectomy affects the bone mass, structure and remodeling in an ovine animal model.</p> <p>Methods</p> <p>Female sheep were arranged into four groups: Control, surgically ovariectomized (Ovx), surgically pinealectomized (Px) and Ovx+Px. Before and 6 months after surgery, iliac crest biopsies were harvested and structural parameters were measured using μCT. Markers of bone formation and resorption were determined. To evaluate long term changes after pinealectomy, bone mineral density (BMD) was analyzed at the distal radius at 0, 3, 9, 18 and 30 months.</p> <p>Results</p> <p>Cancellous bone volume (BV/TV) declined after 6 months by -13.3% Px and -21.5% OvxPx. The bone loss was due to increased trabecular separation as well as decreased thickness. The histomorphometric quantification and determination of collagen degradation products showed increased bone resorption following pinealectomy. Ovariectomy alone results in a transient bone loss at the distal radius followed by continuous increase to baseline levels. The bone resorption activity after pinealectomy causes a bone loss which was not transient, since a continuous decrease in BMD was observed until 30 months.</p> <p>Conclusions</p> <p>The changes after pinealectomy in sheep are indicative of bone loss. Overall, these findings suggest that the pineal gland may influence bone metabolism and that pinealectomy can be used to induce bone loss in sheep.</p