Comparison of Spectra in Unsequenced Species

International audienceWe introduce a new algorithm for the mass spectromet- ric identication of proteins. Experimental spectra obtained by tandem MS/MS are directly compared to theoretical spectra generated from pro- teins of evolutionarily closely related organisms. This work is motivated by the need of a method that allows the identication of proteins of unsequenced species against a database containing proteins of related organisms. The idea is that matching spectra of unknown peptides to very similar MS/MS spectra generated from this database of annotated proteins can lead to annotate unknown proteins. This process is similar to ortholog annotation in protein sequence databases. The difficulty with such an approach is that two similar peptides, even with just one mod- ication (i.e. insertion, deletion or substitution of one or several amino acid(s)) between them, usually generate very dissimilar spectra. In this paper, we present a new dynamic programming based algorithm: Packet- SpectralAlignment. Our algorithm is tolerant to modications and fully exploits two important properties that are usually not considered: the notion of inner symmetry, a relation linking pairs of spectrum peaks, and the notion of packet inside each spectrum to keep related peaks together. Our algorithm, PacketSpectralAlignment is then compared to SpectralAlignment [1] on a dataset of simulated spectra. Our tests show that PacketSpectralAlignment behaves better, in terms of results and execution tim

Anyui Volcano in Chukotka: Age, structure, pecularities of rocks' composition and eruptions

The study of lavas and pyroclastics from Anyui Volcano made it possible to reconstruct succession of its eruption events. The age of the eruption is estimated by isotopic methods to be 0.248 ± 0.030 Ma. It is established that the last episode of volcanic activity in northeastern Russia occurred 0.2‒0.5 Ma ago (in its continental part, 0.2‒0.3 Ma ago). This episode is chronologically close to the last peak in activation of volcanism in the Arctic and Subarctic regions. The absence of features indicating glacial influence on lavas from Anyui Volcano provides grounds for an assumption that no significant glaciations took place in the continental areas of western Chukotka during the last 250 ka

Expected length of the longest common subsequence for large alphabets

We consider the length L of the longest common subsequence of two randomly uniformly and independently chosen n character words over a k-ary alphabet. Subadditivity arguments yield that the expected value of L, when normalized by n, converges to a constant C_k. We prove a conjecture of Sankoff and Mainville from the early 80's claiming that C_k\sqrt{k} goes to 2 as k goes to infinity.Comment: 14 pages, 1 figure, LaTe

Efficacy and safety of left atrial appendage closure in patients with atrial fibrillation and high thromboembolic and bleeding risk

Aim. To compare the incidence of thromboembolic and hemorrhagic events after left atrial appendage occlusion (LAAO) or without prevention of thromboembolic events (TEEs) during prospective follow-up of patients with atrial fibrillation (AF) and a high risk of ischemic stroke (IS) who have contraindications to long-term anticoagulant therapy.Material and methods. The study included 134 patients with AF, a high risk of IS, and contraindications to long-term anticoagulation. Patients were divided into 2 groups as follows: the first group included patients who underwent LAAO (n=74), while the second one — those who did not undergo any TEE prevention (n=60). The follow-up period was 3 years. The cumulative rate of all-cause mortality, IS, transient ischemic attacks (TIA), and systemic embolism (SE) was taken as the primary efficacy endpoint. The primary safety endpoint included major bleeding according to GARFIELD registry criteria.Results.  The rate of composite efficacy endpoint in the LAAO group was significantly lower than in the group without thromboembolic prophylaxis (5,2 vs 17,4 per 100 patient-years; adjusted odds ratio (OR), 4,08; 95% confidence interval (CI): 1,7-9,5; p=0,001). The rate of major bleeding was comparable in both groups (2,4 in the LAAO group vs 1,3 per 100 patient-years in the group without thromboembolic prophylaxis; adjusted OR, 0,55; 95% CI: 0,1-3,09; p=0,509). In addition, the event rate of net clinical benefit (all-cause mortality + ischemic stroke/TIA/SE + major bleeding) in the LAAO group was also significantly lower (5,9 vs 18,2 per 100 patient-years; adjusted OR, 3,0; 95% CI: 1,47-6,36; p=0,003).Conclusion. Among patients with AF and contraindications to long-term anticoagulation after 3 years of follow-up, LAAO demonstrated the significant reduction of cumulative rate of all-cause mortality and non-fatal thromboembolic events. At the same time, the frequency of major bleeding was comparable between the groups, even taking into account access-site bleeding and postoperative antithrombotic therapy (ATT)-associated bleeding in the LAAO group. Further randomized clinical trials are required to confirm these data

Compatibility with cap-products in Tsygan's formality and homological Duflo isomorphism

In this paper we prove, with details and in full generality, that the isomorphism induced on tangent homology by the Shoikhet-Tsygan formality $L_\infty$-quasi-isomorphism for Hochschild chains is compatible with cap-products. This is a homological analog of the compatibility with cup-products of the isomorphism induced on tangent cohomology by Kontsevich formality $L_\infty$-quasi-isomorphism for Hochschild cochains. As in the cohomological situation our proof relies on a homotopy argument involving a variant of {\bf Kontsevich eye}. In particular we clarify the r\^ole played by the {\bf I-cube} introduced in \cite{CR1}. Since we treat here the case of a most possibly general Maurer-Cartan element, not forced to be a bidifferential operator, then we take this opportunity to recall the natural algebraic structures on the pair of Hochschild cochain and chain complexes of an $A_\infty$-algebra. In particular we prove that they naturally inherit the structure of an $A_\infty$-algebra with an $A_\infty$-(bi)module.Comment: The first and second Section on $B_\infty$-algebras and modules have been completely re-written, with new results; partial revision of Section 3; the proofs in Section 4 and 5 have been re-formulated in a more general context; we added Section 8 on globalisatio

Методы экстракорпоральной гемокоррекции в комплексном лечении новой коронавирусной инфекции: обзор возможностей

The objective: to provide pathogenetic justification for the need for extracorporeal blood purification in the new coronavirus infection.Results: the article analyzes guidelines and the first experience of using extracorporeal methods in the new coronavirus infection in different countries. It has been demonstrated that methods of extracorporeal blood purification have complex pleiotropic (multiple) effects and can quickly normalize the level of cytokines and other pathogenic factors, thereby preventing/reducing the severity of organ disorders. The article specifies the criteria for choosing an extracorporeal method, as well as indications for its early and late use.Цель: патогенетическое обоснование необходимости применения экстракорпоральной гемокоррекции при новой коронавирусной инфекции (НКИ).Результаты: проанализированы клинические рекомендации и первый опыт использования экстракорпоральных методов при НКИ в разных странах. Показано, что методы экстракорпоральной гемокоррекции обладают комплексными плейотропными (множественными) эффектами и позволяют быстро нормализовать уровень цитокинов и других факторов патогенеза, тем самым предотвратить/уменьшить степень тяжести органных нарушений. Конкретизированы критерии выбора экстракорпорального метода, а также показания для раннего и позднего применения

Prevention of Cardioembolic Complications in Patients with Atrial Fibrillation: Efficacy and Safety of Left Atrial Appendage Isolation and Oral Anticoagulants

Aim. To study the outcomes frequency and structure in patients with atrial fibrillation (AF) depending on the cardioembolic events preventing method: left atrial appendage (LAA) isolation, direct oral anticoagulants (DOACs) or warfarin.Material and methods. A prospective observational study included patients with AF and high risk of cardioembolic complications and without contraindications to anticoagulants. Patients who refused long-term oral anticoagulants taking underwent LAA isolation, the rest of the patients received DOACs or warfarin. The observation period was 3 years. Mortality, cardioembolic complications and major bleeding (according to GARFIELD criteria) cumulative incidence was assessed.Results. We included 245 patients: 46 patients were treated with LAA isolation, 100 with warfarin, and 99 with DOACs. Multivariate regression analysis demonstrated a statistically significant advantage of LAA occluder in terms of combined endpoint achieving frequency compared to warfarin (hazard ratio [HR] 3.10; 95% confidence interval [CI] 1.01-9.54; p=0.049), and to DOACs (HR 3.44, 95% CI 1.15-10.29; p=0.027). A similar result was obtained for all-cause mortality (HR 5.24; 95% CI 1.12-24.55; p=0.036 and HR 5.58; 95% CI 1.22-25.49; p=0.027, respectively). There were no significant differences in bleeding rates between the groups.Conclusion. This observational study demonstrates the superiority of LAA isolation as a first-line therapy over DOACs and warfarin in patients with AF and high risk of cardioembolic complications. Randomized trials are required to confirm these observations

Optimizing sequencing protocols for leaderboard metagenomics by combining long and short reads.

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewer samples. We term this approach leaderboard metagenome sequencing. To explore protocol optimization for leaderboard metagenomics in real samples, we introduce a benchmark of library prep and sequencing using internal references generated by synthetic long-read technology, allowing us to evaluate high-throughput library preparation methods against gold-standard reference genomes derived from the samples themselves. We introduce a low-cost protocol for high-throughput library preparation and sequencing

A fast algorithm for the multiple genome rearrangement problem with weighted reversals and transpositions

<p>Abstract</p> <p>Background</p> <p>Due to recent progress in genome sequencing, more and more data for phylogenetic reconstruction based on rearrangement distances between genomes become available. However, this phylogenetic reconstruction is a very challenging task. For the most simple distance measures (the breakpoint distance and the reversal distance), the problem is NP-hard even if one considers only three genomes.</p> <p>Results</p> <p>In this paper, we present a new heuristic algorithm that directly constructs a phylogenetic tree w.r.t. the weighted reversal and transposition distance. Experimental results on previously published datasets show that constructing phylogenetic trees in this way results in better trees than constructing the trees w.r.t. the reversal distance, and recalculating the weight of the trees with the weighted reversal and transposition distance. An implementation of the algorithm can be obtained from the authors.</p> <p>Conclusion</p> <p>The possibility of creating phylogenetic trees directly w.r.t. the weighted reversal and transposition distance results in biologically more realistic scenarios. Our algorithm can solve today's most challenging biological datasets in a reasonable amount of time.</p

Механизмы повреждения и защиты клетки при ишемии/реперфузии и экспериментальное обоснование применения препаратов на основе лития в анестезиологии

Pharmaceuticals based on lithium ions have been already used in clinical practice for over 60 years for the treatment of bipolar disorders and remain a basic pharmacological therapy for patients with this disease. In spite of this, the therapeutic mechanisms of action of lithium ions have not been fully investigated. In the past decade, in vitro and in vivo experiments have provided a good deal of data suggesting that lithium ions have previously undescribed neuro-, cardio-, and nephro-protective properties. Numerous investigations have demonstrated that glycogen synthase kinase-3/3, the key enzyme of different pathological and protective signaling pathways, is the target of lithium ions in displaying these effects. This review deals with just these new properties of lithium ions, which make them utterly promising for clinical use in circulatory arrest-associated conditions, which is particularly relevant for anesthesiology and resuscitation. Key words: lithium ions, brain, heart, kidney, postresuscitation disease.Фармакологические препараты на основе ионов лития уже более 60 лет используются в клинической практике для лечения биполярных расстройств и остаются основой фармакотерапии пациентов с этой группой заболеваний. Несмотря на это, терапевтические механизмы действия ионов лития изучены не в полной мере. В течение последних 10 лет в экспериментах in vitro и in vivo было получено множество данных, свидетельствующих о наличии у ионов лития ранее не описанных нейро-, кардио- и нефропротекторных свойств. Основной мишенью ионов лития при реализации этих эффектов является киназа гликогенсинтазы-3в, ключевой фермент различных патологических и защитных сигнальных путей. Данный обзор посвящен новым свойствам ионов лития, делающих их чрезвычайно перспективными для клинического применения при состояниях, связанных с остановкой кровообращения, что особенно актуально для анестезиологии и реаниматологии. Ключевые слова: ионы лития, мозг, сердце, почка, постреанимационная болезнь