L’explicite et l’implicite dans la conception du signe chez Hobbes

L'Auteur dégage et expose d'abord le modèle explicite proposé par Hobbes pour l'analyse des phénomènes sémioti- que, puis le contexte dans lequel ce modèle est élaboré, tout en montrant en quoi cette analyse peut encore intéresser les philosophes du langage contemporains. Il met ensuite en évi- dence les diverses perspectives empruntées par Hobbes dans son analyse, formule les principes sur lesquels elles reposent et décèle les problèmes de cohérence qui en résultent. Il propose enfin une interprétation qui permet de lever certaines contradictions apparentes rencontrées dans l'analyse du mo- dèle proposé par Hobbes en réexaminant le contexte initial de cette analyse et les catégories ontologiques fondamentales qu'elle met en cause.The Author extricates and exposes at first the explicit model proposed by Hobbes to analyse semiotical phenomena, and the context in which this model is developped, showing by the way how this model, in many respects, might still be interesting for contemporary philosophers of language. Then, he reconstructs the approaches adopted by Hobbes, formulates the basic principles on which they rest, and identifies some problems of coherence resulting from the whole approach. He proposes, at last, an interpretation which enables us to solve some apparent contradictions met in the analysis of the model proposed by Hobbes by exploring anew the initial context of this model and the basic ontological categories which are implicated in Hobbes' semiotical analysis

Improving of transitway operating properties

Modern public transport systems are increasingly seen as an important means of promoting the safe mobility of the population, especially in urban areas suffering from growing traffic jams. The Transitway or the new bus system “Bus Rapid Transport” (BRT) is the result of the development of a bus public transport network. In comparison with the subway, this project has obvious advantages: lower cost of network creation, lower cost of rolling stock, mobility, etc. These advantages are manifested, first of all, with the maximum use of passenger capacity of transitways, that is, with the application of three-axles transitways and with their motion on the maximum possible speeds. The purpose of this paper is to present the findings of the transitway motion stability research, which was based on the analysis of solutions of motion differential equations. These equations were compiled with respect to the variables of the longitudinal and transverse velocities of the center of the bus mass and the angular velocities of the bus and of two couplings. As a result of the research, the critical velocity of the three-axles transitway has been determined and factors influencing its numerical value have been analyzed. It has been shown that during the operation of the transitway it is necessary to maintain such pressure in the tires so that, for the selected load on the wheels of the axes of the auto-train, the coefficient of resistance to the lateral separation of the wheels of the steered wheels of the bus and the trailer is smaller than the wheels of uncontrolled axes. The practical value of the research is that this finding will be used for increasing the critical speed vcr of the auto-train

Multiple whole genome alignments and novel biomedical applications at the VISTA portal

The VISTA portal for comparative genomics is designed to give biomedical scientists a unified set of tools to lead them from the raw DNA sequences through the alignment and annotation to the visualization of the results. The VISTA portal also hosts the alignments of a number of genomes computed by our group, allowing users to study the regions of their interest without having to manually download the individual sequences. Here we describe various algorithmic and functional improvements implemented in the VISTA portal over the last 2 years. The VISTA Portal is accessible at http://genome.lbl.gov/vista

Genome-wide changes in protein translation efficiency are associated with autism

We previously proposed that changes in the efficiency of protein translation are associated with autism spectrum disorders (ASDs). This hypothesis connects environmental factors and genetic factors because each can alter translation efficiency. For genetic factors, we previously tested our hypothesis using a small set of ASD-associated genes, a small set of ASD-associated variants, and a statistic to quantify by how much a single nucleotide variant (SNV) in a protein coding region changes translation speed. In this study, we confirm and extend our hypothesis using a published set of 1,800 autism quartets (parents, one affected child and one unaffected child) and genome-wide variants. Then, we extend the test statistic to combine translation efficiency with other possibly relevant variables: ribosome profiling data, presence/absence of CpG dinucleotides, and phylogenetic conservation. The inclusion of ribosome profiling abundances strengthens our results for male–male sibling pairs. The inclusion of CpG information strengthens our results for female–female pairs, giving an insight into the significant gender differences in autism incidence. By combining the single-variant test statistic for all variants in a gene, we obtain a single gene score to evaluate how well a gene distinguishes between affected and unaffected siblings. Using statistical methods, we compute gene sets that have some power to distinguish between affected and unaffected siblings by translation efficiency of gene variants. Pathway and enrichment analysis of those gene sets suggest the importance of Wnt signaling pathways, some other pathways related to cancer, ATP binding, and ATP-ase pathways in the etiology of ASDs

Особливості обрання теоретичного закону розподілу при оцінці надійності зовнішньої ізоляції газонаповнених вимірювальних трансформаторів

In the article, the authors propose a method for estimating the parameters of theoretical distributions for calculating the indicators of operational reliability. In the article, the authors propose a method for estimating the parameters of theoretical distributions for calculating the indicators of the operational reliability of a solid insulating structure of high-voltage devices. Which is a supporting insulating cover for high voltage instrument transformers filled with gas as an insulating liquid. This technique makes it possible to estimate the parameters of a new distribution law, which is chosen on the condition that it does not contradict the existing distribution law with its known parameters. The developed technique makes it possible to obtain the values of the indicators of the operational reliability of high-voltage equipment by determining the parameters of theoretical distributions, if the developer is the data of experimental studies or statistical information as a result of monitoring the operation of insulating structures, taking into account the actual operating conditions of such high-voltage devices.  This makes it possible to take into account the influence of external factors and performance characteristics inherent in instrument transformers, both current and voltage. In the proposed methodology, as an example, a supporting insulating casing is considered, which is during operation in the most unfavorable conditions, such as external pollution, humidification, overvoltage, etc. The theoretical conclusions are confirmed by the results of calculations using the example of the design of a current transformer of the ТОГ-362 series. A more accurate determination of the effectiveness of the proposed method for predicting the parameters of theoretical distribution laws can be achieved by performing an additional series of calculations and experimental tests of specific insulating structures. Thus, it was concluded that it is possible to use the results obtained to assess the operational reliability of both gas-filled instrument transformers and similar high-voltage equipment.В статье авторами предложен метод оценки параметров теоретических распределений для расчёта показателей эксплуатационной надёжности твёрдой изолирующей структуры высоковольтных аппаратов. что представляет собой поддерживающую изолирующую крышку измерительных высоковольтных трансформаторов, заполненных газом в качестве изолирующей жидкости. Эта методика позволяет оценить параметры нового закона распределения, который избирается при условии, что он не противоречит существующему закону распределения с его известными параметрами. Разработанная методика позволяет получить значения показателей эксплуатационной надёжности высоковольтного оборудования путём определения параметров теоретических распределений, если разработчик данные экспериментальных исследований или статистическую информацию в результате мониторинга работы изоляционных конструкций с учётом реальных условий эксплуатации именно таких высоковольтных устройств. Это даёт возможность учесть влияние внешних факторов и эксплуатационных характеристик, присущих измерительным трансформаторам, как тока, так и напряжения. В предлагаемой методике качестве примера рассматривается опорный изоляционный кожух, находящийся при эксплуатации в наиболее неблагоприятных условиях, таких как внешнее загрязнение, увлажнение, перенапряжение и др. Теоретические выводы подтверждаются результатами расчётов на примере конструкции трансформатора тока серии ТОГ-362. Более точное определение эффективности предложенной методики прогнозирования параметров теоретических законов распределения можно достичь путём проведения дополнительной серии расчётов и экспериментальных испытаний конкретных изоляционных конструкций. Таким образом, был сделан вывод о возможности использования полученных результатов для оценки показателей эксплуатационной надёжности как газонаполненных измерительных трансформаторов, так и аналогичного высоковольтного оборудования.В статті авторами запропонований метод оцінки параметрів теоретичних розподілів для розрахунку показників експлуатаційної надійності твердої ізолюючої структури високовольтних апаратів. що являє собою підтримуючу ізолюючую кришку для вимірювальних високовольтних трансформаторів, заповнених газом в якості ізолюючої рідини. Ця методика дозволяє оцінити параметри нового закону розподілу, який обирається за умови, що він не суперечить існуючим законом розподілу з його відомими параметрами. Розроблена методика дозволяє отримати значення показників експлуатаційної надійності високовольтного обладнання шляхом визначення параметрів теоретичних розподілів, якщо розробник має дані експериментальних досліджень або статистичну інформацію в результаті моніторингу роботи ізоляційних конструкцій з урахуванням реальних умов експлуатації саме таких високовольтних пристроїв. Це дає можливість врахувати вплив зовнішніх факторів і експлуатаційних характеристик, властивих вимірювальним трансформаторам, як струму, так і напруги. У запропонованій методиці як приклад розглядається опорний ізоляційний кожух, що знаходиться під час експлуатації в найбільш несприятливих умовах, таких як зовнішнє забруднення, зволоження, перенапруження та ін. Теоретичні висновки підтверджуються результатами розрахунків на прикладі конструкції трансформатора струму серії ТОГ-362. Більш точне визначення ефективності запропонованої методики прогнозування параметрів теоретичних законів розподілу можна досягти проведенням додаткової серії розрахунків та експериментальних випробувань конкретних ізоляційних конструкцій. Таким чином, був зроблений висновок про можливість використання отриманих результатів для оцінки показників експлуатаційної надійності як газонаповнених вимірювальних трансформаторів, так і аналогічного високовольтного обладнання

Analysis of transverse stability parameters of hybrid buses with active trailers

The objective of the article is to determine the transverse stability indexes of hinged-connected buses by applying the computation and analytical method. The transverse stability parameters of hybrid buses with active trailers are analyzed. Based on the transverse stability parameters (the angles of the roll and redistribution of loads on the sides), the analytical dependences are developed. The dependences describe the movement of the parts of hinged-connected buses in the vertical plane. Considering the action of longitudinal and transverse forces, the roll angles of the bus and the trailer were determined. The limiting angle of the side roll of the bus rollover was found to be амах = 27.560мах, and the trailer rollover - амах = 30.210. The obtained transverse stability indexes of hinged-connected buses with a hybrid power plant testify to the compliance with the standard DSTU UN / ECE R 111-00

Mutational signatures and mutable motifs in cancer genomes

Cancer is a genetic disorder, meaning that a plethora of different mutations, whether somatic or germ line, underlie the etiology of the ‘Emperor of Maladies’. Point mutations, chromosomal rearrangements and copy number changes, whether they have occurred spontaneously in predisposed individuals or have been induced by intrinsic or extrinsic (environmental) mutagens, lead to the activation of oncogenes and inactivation of tumor suppressor genes, thereby promoting malignancy. This scenario has now been recognized and experimentally confirmed in a wide range of different contexts. Over the past decade, a surge in available sequencing technologies has allowed the sequencing of whole genomes from liquid malignancies and solid tumors belonging to different types and stages of cancer, giving birth to the new field of cancer genomics. One of the most striking discoveries has been that cancer genomes are highly enriched with mutations of specific kinds. It has been suggested that these mutations can be classified into ‘families’ based on their mutational signatures. A mutational signature may be regarded as a type of base substitution (e.g. C:G to T:A) within a particular context of neighboring nucleotide sequence (the bases upstream and/or downstream of the mutation). These mutational signatures, supplemented by mutable motifs (a wider mutational context), promise to help us to understand the nature of the mutational processes that operate during tumor evolution because they represent the footprints of interactions between DNA, mutagens and the enzymes of the repair/replication/modification pathway

DNA methylation, deamination, and translesion synthesis combine to generate footprint mutations in cancer driver genes in B-cell derived lymphomas and other cancers

Cancer genomes harbor numerous genomic alterations and many cancers accumulate thousands of nucleotide sequence variations. A prominent fraction of these mutations arises as a consequence of the off-target activity of DNA/RNA editing cytosine deaminases followed by the replication/repair of edited sites by DNA polymerases (pol), as deduced from the analysis of the DNA sequence context of mutations in different tumor tissues. We have used the weight matrix (sequence profile) approach to analyze mutagenesis due to Activation Induced Deaminase (AID) and two error-prone DNA polymerases. Control experiments using shuffled weight matrices and somatic mutations in immunoglobulin genes confirmed the power of this method. Analysis of somatic mutations in various cancers suggested that AID and DNA polymerases η and θ contribute to mutagenesis in contexts that almost universally correlate with the context of mutations in A:T and G:C sites during the affinity maturation of immunoglobulin genes. Previously, we demonstrated that AID contributes to mutagenesis in (de)methylated genomic DNA in various cancers. Our current analysis of methylation data from malignant lymphomas suggests that driver genes are subject to different (de)methylation processes than non-driver genes and, in addition to AID, the activity of pols η and θ contributes to the establishment of methylation-dependent mutation profiles. This may reflect the functional importance of interplay between mutagenesis in cancer and (de)methylation processes in different groups of genes. The resulting changes in CpG methylation levels and chromatin modifications are likely to cause changes in the expression levels of driver genes that may affect cancer initiation and/or progression

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella