Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames.

Mammalian gene expression displays widespread circadian oscillations. Rhythmic transcription underlies the core clock mechanism, but it cannot explain numerous observations made at the level of protein rhythmicity. We have used ribosome profiling in mouse liver to measure the translation of mRNAs into protein around the clock and at high temporal and nucleotide resolution. We discovered, transcriptome-wide, extensive rhythms in ribosome occupancy and identified a core set of approximately 150 mRNAs subject to particularly robust daily changes in translation efficiency. Cycling proteins produced from nonoscillating transcripts revealed thus-far-unknown rhythmic regulation associated with specific pathways (notably in iron metabolism, through the rhythmic translation of transcripts containing iron responsive elements), and indicated feedback to the rhythmic transcriptome through novel rhythmic transcription factors. Moreover, estimates of relative levels of core clock protein biosynthesis that we deduced from the data explained known features of the circadian clock better than did mRNA expression alone. Finally, we identified uORF translation as a novel regulatory mechanism within the clock circuitry. Consistent with the occurrence of translated uORFs in several core clock transcripts, loss-of-function of Denr, a known regulator of reinitiation after uORF usage and of ribosome recycling, led to circadian period shortening in cells. In summary, our data offer a framework for understanding the dynamics of translational regulation, circadian gene expression, and metabolic control in a solid mammalian organ.

Semantic domain and grammatical class effects in the picture-word interference paradigm

The role of grammatical class in lexical access and representation is still not well understood. Grammatical effects obtained in picture-word interference experiments have been argued to show the operation of grammatical constraints during lexicalization when syntactic integration is required by the task. Alternative views hold that the ostensibly grammatical effects actually derive from the coincidence of semantic and grammatical differences between lexical candidates. We present three picture-word interference experiments conducted in Spanish. In the first two, the semantic relatedness (related or unrelated) and the grammatical class (nouns or verbs) of the target and the distracter were manipulated in an infinitive form action naming task in order to disentangle their contributions to verb lexical access. In the third experiment, a possible confound between grammatical class and semantic domain (objects or actions) was eliminated by using action-nouns as distracters. A condition in which participants were asked to name the action pictures using an inflected form of the verb was also included to explore whether the need of syntactic integration modulated the appearance of grammatical effects. Whereas action-words (nouns or verbs), but not object-nouns, produced longer reaction times irrespective of their grammatical class in the infinitive condition, only verbs slowed latencies in the inflected form condition. Our results suggest that speech production relies on the exclusion of candidate responses that do not fulfil task-pertinent criteria like membership in the appropriate semantic domain or grammatical class. Taken together, these findings are explained by a response-exclusion account of speech output. This and alternative hypotheses are discussed.

Of pearls and pigs : a conceptual-semantic Tiernet approach to formal representation of structure and variation of phraseological units

"Helmiä sioille", pärlor för svin, säger man på finska om någonting bra och fint som tas emot av en mottagare som inte vill eller har ingen förmåga att förstå, uppskatta eller utnyttja hela den potential som finns hos det mottagna föremålet, är ointresserad av den eller gillar den inte. För sådana relativt stabila flerordiga uttryck, som är lagrade i språkbrukarnas minnen och som demonstrerar olika slags oregelbundna drag i sin struktur använder man inom lingvistiken bl.a. termerna "idiom" eller "fraseologiska enheter". Som en oregelbundenhet kan man t.ex. beskriva det faktum att betydelsen hos uttrycket inte är densamma som man skulle komma till ifall man betraktade det som en vanlig regelbunden fras. En annan oregelbundenhet, som idiomforskare har observerat, ligger i den begränsade förmågan att varieras i form och betydelse, som många idiom har jämfört med regelbundna fraser. Därför talas det ofta om "grundform" och "grundbetydelse" hos idiom och variationen avses som avvikelse från dessa. Men när man tittar på ett stort antal förekomstexempel av idiom i språkbruk, märker man att många av dem tillåter variation, t.o.m. i sådan utsträckning att gränserna mellan en variant och en "grundform" suddas ut, och istället för ett idiom råkar vi plötsligt på en "familj" av flera besläktade uttryck. Allt detta väcker frågan om hur dessa uttryck egentligen ska vara representerade i språket. I avhandlingen utförs en kritisk granskning av olika tidigare tillvägagångssätt att beskriva fraseologiska enheter i syfte att klargöra vilka svårigheter deras struktur och variation erbjuder för den lingvistiska teorin. Samtidigt presenteras ett alternativt sätt att beskriva dessa uttryck. En systematisk och formell modell som utvecklas i denna avhandling integrerar en beskrivning av idiom på många olika språkliga nivåer och skildrar deras variation i form av ett nätverk och som ett resultat av samspel mellan idiomets struktur och kontexter där det förekommer, samt av interaktion med andra fasta uttryck. Modellen bygger på en fördjupande, språkbrukbaserad analys av det finska idiomet "X HEITTÄÄ HELMIÄ SIOILLE" (X kastar pärlor för svin).

Expectations, frames and practices of genetic counselling in different contexts of genetic testing

Genetic counselling is a process in which the counsellee receives information and support concerning a genetic disease. This study examines the genetic counselling attached to genetic testing. Since genetic information is increasing alongside new testing technologies and the situations faced at the genetic clinics will therefore be more diverse, it is essential to assess what the expectations directed at genetic counselling are. It is also important to compare how they face the current counselling practices. In this study, the expectations, frames and practices of genetic counselling in different contexts of genetic testing were examined from three different perspectives: First, international guidelines covering genetic counselling were analysed to summarise what is expected from genetic counselling and to study how genetic information is framed. Second, national experts in European countries were asked about the regulations and practices of genetic counselling in their country. Finally, ten counsellees who had visited a genetic clinic were interviewed to analyse their expectations and experiences. The counsellees’ perspective was also approached through the background review of the previous studies on counsellees’ experiences. On the basis of the study, there are basic elements that are expected to be covered in genetic counselling from all perspectives. However, the views concerning bioethics, genetic exceptionalism and psychosocial aspects vary depending on the perspective and on the individual situation. Since there are sometimes more differences than similarities between genetic tests, no universal recommendations for counselling can be applied. The practices of genetic counselling should be defined situationally, emphasising the individual needs over the genes.

Semantic and fuzzy modelling for human behaviour recognition in smart spaces : a case study on ambient assisted living.

Human activity recognition in everyday environments is a critical, but challenging task in Ambient Intelligence applications to achieve proper Ambient Assisted Living, and key challenges still remain to be dealt with to realize robust methods. One of the major limitations of the Ambient Intelligence systems today is the lack of semantic models of those activities on the environment, so that the system can recognize the speci c activity being performed by the user(s) and act accordingly. In this context, this thesis addresses the general problem of knowledge representation in Smart Spaces. The main objective is to develop knowledge-based models, equipped with semantics to learn, infer and monitor human behaviours in Smart Spaces. Moreover, it is easy to recognize that some aspects of this problem have a high degree of uncertainty, and therefore, the developed models must be equipped with mechanisms to manage this type of information. A fuzzy ontology and a semantic hybrid system are presented to allow modelling and recognition of a set of complex real-life scenarios where vagueness and uncertainty are inherent to the human nature of the users that perform it. The handling of uncertain, incomplete and vague data (i.e., missing sensor readings and activity execution variations, since human behaviour is non-deterministic) is approached for the rst time through a fuzzy ontology validated on real-time settings within a hybrid data-driven and knowledgebased architecture. The semantics of activities, sub-activities and real-time object interaction are taken into consideration. The proposed framework consists of two main modules: the low-level sub-activity recognizer and the high-level activity recognizer. The rst module detects sub-activities (i.e., actions or basic activities) that take input data directly from a depth sensor (Kinect). The main contribution of this thesis tackles the second component of the hybrid system, which lays on top of the previous one, in a superior level of abstraction, and acquires the input data from the rst module's output, and executes ontological inference to provide users, activities and their in uence in the environment, with semantics. This component is thus knowledge-based, and a fuzzy ontology was designed to model the high-level activities. Since activity recognition requires context-awareness and the ability to discriminate among activities in di erent environments, the semantic framework allows for modelling common-sense knowledge in the form of a rule-based system that supports expressions close to natural language in the form of fuzzy linguistic labels. The framework advantages have been evaluated with a challenging and new public dataset, CAD-120, achieving an accuracy of 90.1% and 91.1% respectively for low and high-level activities. This entails an improvement over both, entirely data-driven approaches, and merely ontology-based approaches. As an added value, for the system to be su ciently simple and exible to be managed by non-expert users, and thus, facilitate the transfer of research to industry, a development framework composed by a programming toolbox, a hybrid crisp and fuzzy architecture, and graphical models to represent and con gure human behaviour in Smart Spaces, were developed in order to provide the framework with more usability in the nal application. As a result, human behaviour recognition can help assisting people with special needs such as in healthcare, independent elderly living, in remote rehabilitation monitoring, industrial process guideline control, and many other cases. This thesis shows use cases in these areas.

Time frames. Negotiating Cultural History

Time Frames brings together a group of cultural historians studying several different periods and locations in the history of Western culture, to discuss the temporal structures which historical studies live by. How do we construct chronologies and temporal sequences? How should we approach the discontinuity and particularity of the past, and its periodization? Deploying ideas and frames from three contemporary conceptual debates - spatial organisation, constructions of experience, and the cultural embeddedness of individual agency - the writers of this book propose methods of historicizing and explore what cultural history is about today.

A lexical semantic study of Dene Suliné, an Athabaskan language

Cette thèse constitue une étude systématique du lexique du déné sųłiné, une langue athabaskane du nord-ouest canadien. Elle présente les définitions et les patrons de combinatoire syntaxique et lexicale de plus de 200 unités lexicales, lexèmes et phrasèmes, qui représentent une partie importante du vocabulaire déné sųłiné dans sept domaines: les émotions, le caractère humain, la description physique des entités, le mouvement des êtres vivants, la position des entités, les conditions atmospheriques et les formations topologiques, en les comparant avec le vocubulaire équivalent de l'anglais. L’approche théorique choisie est la Théorie Sens-Texte (TST), une approche formelle qui met l’accent sur la description sémantique et lexicographique empiriques. La présente recherche relève d'importantes différences entre le lexique du déné sųłiné et celui de l'anglais à tous les niveaux: dans la correspondence entre la représentation conceptuelle, considérée (quasi-)extralinguistique, et la structure sémantique; dans les patrons de lexicalisation des unités lexicales, et dans les patrons de combinatoire syntaxique et lexicale, qui montrent parfois des traits propres au déné sųłiné intéressants.

Criteria for the validation of specialized verb equivalents : application in bilingual terminography

Multilingual terminological resources do not always include valid equivalents of legal terms for two main reasons. Firstly, legal systems can differ from one language community to another and even from one country to another because each has its own history and traditions. As a result, the non-isomorphism between legal and linguistic systems may render the identification of equivalents a particularly challenging task. Secondly, by focusing primarily on the definition of equivalence, a notion widely discussed in translation but not in terminology, the literature does not offer solid and systematic methodologies for assigning terminological equivalents. As a result, there is a lack of criteria to guide both terminologists and translators in the search and validation of equivalent terms. This problem is even more evident in the case of predicative units, such as verbs. Although some terminologists (L‘Homme 1998; Lerat 2002; Lorente 2007) have worked on specialized verbs, terminological equivalence between units that belong to this part of speech would benefit from a thorough study. By proposing a novel methodology to assign the equivalents of specialized verbs, this research aims at defining validation criteria for this kind of predicative units, so as to contribute to a better understanding of the phenomenon of terminological equivalence as well as to the development of multilingual terminography in general, and to the development of legal terminography, in particular. The study uses a Portuguese-English comparable corpus that consists of a single genre of texts, i.e. Supreme Court judgments, from which 100 Portuguese and 100 English specialized verbs were selected. The description of the verbs is based on the theory of Frame Semantics (Fillmore 1976, 1977, 1982, 1985; Fillmore and Atkins 1992), on the FrameNet methodology (Ruppenhofer et al. 2010), as well as on the methodology for compiling specialized lexical resources, such as DiCoInfo (L‘Homme 2008), developed in the Observatoire de linguistique Sens-Texte at the Université de Montréal. The research reviews contributions that have adopted the same theoretical and methodological framework to the compilation of lexical resources and proposes adaptations to the specific objectives of the project. In contrast to the top-down approach adopted by FrameNet lexicographers, the approach described here is bottom-up, i.e. verbs are first analyzed and then grouped into frames for each language separately. Specialized verbs are said to evoke a semantic frame, a sort of conceptual scenario in which a number of mandatory elements (core Frame Elements) play specific roles (e.g. ARGUER, JUDGE, LAW), but specialized verbs are often accompanied by other optional information (non-core Frame Elements), such as the criteria and reasons used by the judge to reach a decision (statutes, codes, previous decisions). The information concerning the semantic frame that each verb evokes was encoded in an xml editor and about twenty contexts illustrating the specific way each specialized verb evokes a given frame were semantically and syntactically annotated. The labels attributed to each semantic frame (e.g. [Compliance], [Verdict]) were used to group together certain synonyms, antonyms as well as equivalent terms. The research identified 165 pairs of candidate equivalents among the 200 Portuguese and English terms that were grouped together into 76 frames. 71% of the pairs of equivalents were considered full equivalents because not only do the verbs evoke the same conceptual scenario but their actantial structures, the linguistic realizations of the actants and their syntactic patterns were similar. 29% of the pairs of equivalents did not entirely meet these criteria and were considered partial equivalents. Reasons for partial equivalence are provided along with illustrative examples. Finally, the study describes the semasiological and onomasiological entry points that JuriDiCo, the bilingual lexical resource compiled during the project, offers to future users.

The Relation Between Depressive Symptoms and Semantic Memory in Amnestic Mild Cognitive Impairment and in Late-Life Depression

Semantic deficits have been documented in the prodromal phase of Alzheimer’s disease, but it is unclear whether these deficits are associated with non-cognitive manifestations. For instance, recent evidence indicates that cognitive deficits in elders with amnestic mild cognitive impairment (aMCI) are modulated by concomitant depressive symptoms. The purposes of this study were to (i) investigate if semantic memory impairment in aMCI is modulated according to the presence (aMCI-D group) or absence (aMCI group) of depressive symptoms, and (ii) compare semantic memory performance of aMCI and aMCI-D groups to that of patients with late-life depression (LLD). Seventeen aMCI, 16 aMCI-D, 15 LLD, and 26 healthy control participants were administered a semantic questionnaire assessing famous person knowledge. Results showed that performance of aMCI-D patients was impaired compared to the control and LLD groups. However, in the aMCI group performance was comparable to that of all other groups. Overall, these findings suggest that semantic deficits in aMCI are somewhat associated with the presence of concomitant depressive symptoms. However, depression alone cannot account solely for the semantic deficits since LLD patients showed no semantic memory impairment in this study. Future studies should aim at clarifying the association between depression and semantic deficits in older adults meeting aMCI criteria.

Neural changes associated with semantic processing in healthy aging despite intact behavioral performance

Semantic memory recruits an extensive neural network including the left inferior prefrontal cortex (IPC) and the left temporoparietal region, which are involved in semantic control processes, as well as the anterior temporal lobe region (ATL) which is considered to be involved in processing semantic information at a central level. However, little is known about the underlying neuronal integrity of the semantic network in normal aging. Young and older healthy adults carried out a semantic judgment task while their cortical activity was recorded using magnetoencephalography (MEG). Despite equivalent behavioral performance, young adults activated the left IPC to a greater extent than older adults, while the latter group recruited the temporoparietal region bilaterally and the left ATL to a greater extent than younger adults. Results indicate that significant neuronal changes occur in normal aging, mainly in regions underlying semantic control processes, despite an apparent stability in performance at the behavioral level.

A Study Of Frames In The Fuzzy And Intuitionist Fuzzy Contexts

The fuzzy set theory has a wider scope of applicability than classical set theory in solving various problems. Fuzzy set theory in the last three decades as a formal theory which got formalized by generalizing the original ideas and concepts in classical mathematical areas and as a very powerful modeling language, that can cope with a large fraction of uncertainties of real life situations. In Intuitionistic Fuzzy sets a new component degree of non membership in addition to the degree of membership in the case of fuzzy sets with the requirement that their sum be less than or equal to one. The main objective of this thesis is to study frames in Fuzzy and Intuitionistic Fuzzy contexts. The thesis proved some results such as ifµ is a fuzzy subset of a frame F, then µ is a fuzzy frame of F iff each non-empty level subset µt of µ is a subframe of F, the category Fuzzfrm of fuzzy frames has products and the category Fuzzfrm of fuzzy frames is complete. It define a fuzzy-quotient frame of F to be a fuzzy partition of F, that is, a subset of IF and having a frame structure with respect to new operations and study the notion of intuitionistic fuzzy frames and obtain some results and introduce the concept of Intuitionistic fuzzy Quotient frames. Finally it establish the categorical link between frames and intuitionistic fuzzy topologies.

Numerical Investigations on Soil Structure Interaction of Multistorey Frames

Frames are the most widely used structural system for multistorey buildings. A building frame is a three dimensional discrete structure consisting of a number of high rise bays in two directions at right angles to each other in the vertical plane. Multistorey frames are a three dimensional lattice structure which are statically indeterminate. Frames sustain gravity loads and resist lateral forces acting on it. India lies at the north westem end of the Indo-Australian tectonic plate and is identified as an active tectonic area. Under horizontal shaking of the ground, horizontal inertial forces are generated at the floor levels of a multistorey frame. These lateral inertia forces are transferred by the floor slab to the beams, subsequently to the columns and finally to the soil through the foundation system. There are many parameters that affect the response of a structure to ground excitations such as, shape, size and geometry of the structure, type of foundation, soil characteristics etc. The Soil Structure Interaction (SS1) effects refer to the influence of the supporting soil medium on the behavior of the structure when it is subjected to different types of loads. Interaction between the structure and its supporting foundation and soil, which is a complete system, has been modeled with finite elements. Numerical investigations have been carried out on a four bay, twelve storeyed regular multistorey frame considering depth of fixity at ground level, at characteristic depth of pile and at full depth. Soil structure interaction effects have been studied by considering two models for soil viz., discrete and continuum. Linear static analysis has been conducted to study the interaction effects under static load. Free vibration analysis and further shock spectrum analysis has been conducted to study the interaction effects under time dependent loads. The study has been extended to four types of soil viz., laterite, sand, alluvium and layered.The structural responses evaluated in the finite element analysis are bending moment, shear force and axial force for columns, and bending moment and shear force for beams. These responses increase with increase in the founding depth; however these responses show minimal increase beyond the characteristic length of pile. When the soil structure interaction effects are incorporated in the analysis, the aforesaid responses of the frame increases upto the characteristic depth and decreases when the frame has been analysed for the full depth. It has been observed that shock spectrum analysis gives wide variation of responses in the frame compared to linear elastic analysis. Both increase and decrease in responses have been observed in the interior storeys. The good congruence shown by the two finite element models viz., discrete and continuum in linear static analysis has been absent in shock spectrum analysis.