Synthesis of Janus compounds for the recognition of G-U mismatched nucleobase pairs

The design and synthesis of two Janus-type heterocycles with the capacity to simultaneously recognize guanine and uracyl in G-U mismatched pairs through complementary hydrogen bond pairing is described. Both compounds were conveniently functionalized with a carboxylic function and efficiently attached to a tripeptide sequence by using solid-phase methodologies. Ligands based on the derivatization of such Janus compounds with a small aminoglycoside, neamine, and its guanidinylated analogue have been synthesized, and their interaction with Tau RNA has been investigated by using several biophysical techniques, including UV-monitored melting curves, fluorescence titration experiments, and 1H NMR. The overall results indicated that Janus-neamine/guanidinoneamine showed some preference for the +3 mutated RNA sequence associated with the development of some tauopathies, although preliminary NMR studies have not confirmed binding to G-U pairs. Moreover, a good correlation has been found between the RNA binding affinity of such Janus-containing ligands and their ability to stabilize this secondary structure upon complexation.

Les artistes visuels au Yémen, du soutien à la contestation de l'ordre politique

Cette thèse appréhende les rapports au politique des artistes visuels yéménites dans un contexte de domination, recouvrant trois États (les deux républiques qui précédent l'unification du Yémen et la république actuelle créée en 1990, jusqu'en 2015). En étudiant la domination en acte à travers une démarche ethnographique, ce travail interroge les conditions de production et d'action des artistes en soutien ou en contestation au régime, comme au cours du moment révolutionnaire de 2011. On observe ainsi le processus de politisation des mondes de l'art au Yémen contemporain, processus compris en tant qu'acquisition d'une signification politique par la pratique artistique et par les réseaux de relations entretenus par les artistes visuels. Ces requalifications de leur travail ou de leurs actions se font dans un contexte traversé par des luttes concurrentielles pour la répartition du pouvoir, aussi bien internes et propres à leurs mondes d'activité, qu'externes et en relation à l'espace politique institutionnel. La politisation des mondes de l'art apparaît dès lors moins comme un instrument d'accès à cet espace qu'une voie pour accéder à plus de visibilité, à la reconnaissance, et à un meilleur positionnement dans les rapports agonistiques qui configurent ces mondes. -- This thesis focuses on the study of Yemeni visual artists' relation to politics in a context of domination, covering three States (the two republics that precede Yemen's unification and the current republic established in 1990, until 2015). Studying domination in action througli an ethnographic approach, this work questions artists' conditions of production and of action in support to or in contestation of the regime- as in the case of the revolutionary period of 2011. It observes the politicization of art worlds in contemporary Yemen, a process understood as the acquisition of a political significance as observed in the artistic practice and in the dynamic networks that artists maintain. The requalification and reclassification of their work and their actions that results from the politicization of art worlds, takes place in a context of competitive struggles over distribution and access to sites of power. Such conflict over power occurs within their own worlds of activity as well as outside them and in relation to the domain of institutional politics. This thesis contends that the politicization of art worlds is more of a means to access visibility and recognition than a resource to participate in the political field. Through the politicization of art, artists are able to better position themselves within the agonistic relations that exist within art worlds.

A genotypic mutation system measuring mutations in restriction recognition sequences.

The RFLP/PCR approach (restriction fragment length polymorphism/polymerase chain reaction) to genotypic mutation analysis described here measures mutations in restriction recognition sequences. Wild-type DNA is restricted before the resistant, mutated sequences are amplified by PCR and cloned. We tested the capacity of this experimental design to isolate a few copies of a mutated sequence of the human c-Ha-ras1 gene from a large excess of wild-type DNA. For this purpose we constructed a 272 bp fragment with 2 mutations in the PvuII recognition sequence 1727-1732 and studied the rescue by RFLP/PCR of a few copies of this 'PvuII mutant standard'. Following amplification with Taq-polymerase and cloning into lambda gt10, plaques containing wild-type sequence, PvuII mutant standard or Taq-polymerase induced bp changes were quantitated by hybridization with specific oligonucleotide probes. Our results indicate that 10 PvuII mutant standard copies can be rescued from 10(8) to 10(9) wild-type sequences. Taq polymerase errors originating from unrestricted, residual wild-type DNA were sequence dependent and consisted mostly of transversions originating at G.C bp. In contrast to a doubly mutated 'standard' the capacity to rescue single bp mutations by RFLP/PCR is limited by Taq-polymerase errors. Therefore, we assessed the capacity of our protocol to isolate a G to T transversion mutation at base pair 1698 of the MspI-site 1695-1698 of the c-Ha-ras1 gene from excess wild-type ras1 DNA. We found that 100 copies of the mutated ras1 fragment could be readily rescued from 10(8) copies of wild-type DNA.

Causality and contagion in peripheral EMU public debt markets: a dynamic approach

Our research aims to analyze the causal relationships in the behavior of public debt issued by peripheral member countries of the European Economic and Monetary Union -EMU-, with special emphasis on the recent episodes of crisis triggered in the eurozone sovereign debt markets since 2009. With this goal in mind, we make use of a database of daily frequency of yields on 10-year government bonds issued by five EMU countries -Greece, Ireland, Italy, Portugal and Spain-, covering the entire history of the EMU from its inception on 1 January 1999 until 31 December 2010. In the first step, we explore the pair-wise causal relationship between yields, both for the whole sample and for changing subsamples of the data, in order to capture the possible time-varying causal relationship. This approach allows us to detect episodes of contagion between yields on bonds issued by different countries. In the second step, we study the determinants of these contagion episodes, analyzing the role played by different factors, paying special attention to instruments that capture the total national debt -domestic and foreign- in each country.

Flexible Multibody Simulation Approach in the Dynamic Analysis of Bone Strains Activity

The objective of this study is to show that bone strains due to dynamic mechanical loading during physical activity can be analysed using the flexible multibody simulation approach. Strains within the bone tissue play a major role in bone (re)modeling. Based on previous studies, it has been shown that dynamic loading seems to be more important for bone (re)modeling than static loading. The finite element method has been used previously to assess bone strains. However, the finite element method may be limited to static analysis of bone strains due to the expensive computation required for dynamic analysis, especially for a biomechanical system consisting of several bodies. Further, in vivo implementation of strain gauges on the surfaces of bone has been used previously in order to quantify the mechanical loading environment of the skeleton. However, in vivo strain measurement requires invasive methodology, which is challenging and limited to certain regions of superficial bones only, such as the anterior surface of the tibia. In this study, an alternative numerical approach to analyzing in vivo strains, based on the flexible multibody simulation approach, is proposed. In order to investigate the reliability of the proposed approach, three 3-dimensional musculoskeletal models where the right tibia is assumed to be flexible, are used as demonstration examples. The models are employed in a forward dynamics simulation in order to predict the tibial strains during walking on a level exercise. The flexible tibial model is developed using the actual geometry of the subject’s tibia, which is obtained from 3 dimensional reconstruction of Magnetic Resonance Images. Inverse dynamics simulation based on motion capture data obtained from walking at a constant velocity is used to calculate the desired contraction trajectory for each muscle. In the forward dynamics simulation, a proportional derivative servo controller is used to calculate each muscle force required to reproduce the motion, based on the desired muscle contraction trajectory obtained from the inverse dynamics simulation. Experimental measurements are used to verify the models and check the accuracy of the models in replicating the realistic mechanical loading environment measured from the walking test. The predicted strain results by the models show consistency with literature-based in vivo strain measurements. In conclusion, the non-invasive flexible multibody simulation approach may be used as a surrogate for experimental bone strain measurement, and thus be of use in detailed strain estimation of bones in different applications. Consequently, the information obtained from the present approach might be useful in clinical applications, including optimizing implant design and devising exercises to prevent bone fragility, accelerate fracture healing and reduce osteoporotic bone loss.

Gli altri noi : Rom e residenti nella Svizzera italiana : etnografia e mediazione

Cette recherche porte sur les roms (vlach) qui séjournent périodiquement en Suisse italienne, en camping-cars ou en caravanes, pratiquant un semi- nomadisme lié à des motivations principalement économiques, mais également familiales et religieuses. Elle poursuit simultanément deux objectifs. Le premier est lié à un souci de médiation culturelle, qui rejoint les réflexions sur la façon de gérer au mieux les conflits entre les diverses composantes du vivre ensemble. Le second vise à approfondir la connaissance des populations roms concernées (lovara, éurara ou kalderasa, de nationalités italienne, française et espagnole). Les deux objectifs sont évidemment reliés, car comprendre les dynamiques conflictuelles exige la connaissance approfondie des acteurs en interaction. Les relations entre résidents tessinois et roms ont évolué dans le temps, avec des oscillations entre le pôle du refus et celui de l'attraction, entre rejet et reconnaissance, méfiance et confiance. Ces variations historiques renvoient à un fondement commun, à une dynamique des oppositions réciproques. L'analyse anthropologique a fait apparaître le rôle ambivalent du conflit dans la production et la reproduction de la relation d'altérité. L'exclusion des roms fournit à certaines tendances politiques locales l'occasion d'apparaître comme les protecteurs des résidents contre les étrangers ; inversement, l'opposition des roms aux gaiés leur permet de resserrer leur communauté et de prévenir l'assimilation. La médiation culturelle peut espérer gérer cette dynamique relationnelle, certainement pas la faire disparaître. Le modèle intégratif traditionnel de l'État- nation se révèle trop étroit pour accueillir la culture rom. Casser la résistance des roms envers le travail salarié et envers la scolarisation obligatoire, entraver leur semi-nomadisme (qui incite aussi leurs rencontres familiales et religieuses), refuser de reconnaître leur organe de justice interne et leur langue, tout cela ne ferait que concourir à leur disparition culturelle. Les roms sont conscients de ces possibilités, raison pour laquelle ils maintiennent une ambivalence relationnelle avec les ga£és, quitte à apparaître comme des « tsiganes indésirables ». Abstract : This research focuses on the Roma people (Vlach) who periodically stay in Italian Switzerland in caravans or camper vans, practising a semi-nomadic lifestyle - a choice based mainly on economic imperatives but also on familial and religious grounds. This study will address two objectives at the same time. The first involves cultural mediation, and considers the best way to manage the existing conflicts between the cultural components of the social environment. The second aims to increase knowledge of the Roma populations under examination - the Italian, French and Spanish Lovara, Éurara or Kalderasa. The two objectives are clearly linked, as a deeper understanding of the people involved is vital if we are to increase understanding of the dynamics of confrontation. The relationships between the residents of the Ticino area and the Roma people have evolved over time, oscillating in varying degrees between rejection and attraction, confrontation and recognition, suspicion and trust. These variations spring from a common base, a dynamic shaped by mutual opposition. The anthropological analysis highlights the ambivalent role of conflict in the production and reproduction of relations of otherness. Excluding the Roma has given some local politicians the opportunity to position themselves as protectors of residents against foreigners. Inversely, the Roma people's opposition to the Gazé strengthens links within their community and prevents assimilation. Cultural mediation may aspire to manage this relational dynamic, but not abolish it. The traditional integrative model of the nation-state has shown itself to be too restrictive to accommodate the Romani culture. Rejecting the Roma's resistance to salaried work and obligatory schooling, obstructing their semi-nomadic lifestyle (one that also involves family and religious assemblies) and refusing to recognise their traditional courts and mother tongue, all that can only contribute to the dilution of their cultural heritage. The Roma are fully aware of these possibilities, which is why they retain a relational ambivalence in their dealings with the Gazé, at the cost of appearing to be "undesirable gypsies".

Lexical Influences on Spoken Spondaic Word Recognition in Hearing-Impaired Patients.

Top-down contextual influences play a major part in speech understanding, especially in hearing-impaired patients with deteriorated auditory input. Those influences are most obvious in difficult listening situations, such as listening to sentences in noise but can also be observed at the word level under more favorable conditions, as in one of the most commonly used tasks in audiology, i.e., repeating isolated words in silence. This study aimed to explore the role of top-down contextual influences and their dependence on lexical factors and patient-specific factors using standard clinical linguistic material. Spondaic word perception was tested in 160 hearing-impaired patients aged 23-88 years with a four-frequency average pure-tone threshold ranging from 21 to 88 dB HL. Sixty spondaic words were randomly presented at a level adjusted to correspond to a speech perception score ranging between 40 and 70% of the performance intensity function obtained using monosyllabic words. Phoneme and whole-word recognition scores were used to calculate two context-influence indices (the j factor and the ratio of word scores to phonemic scores) and were correlated with linguistic factors, such as the phonological neighborhood density and several indices of word occurrence frequencies. Contextual influence was greater for spondaic words than in similar studies using monosyllabic words, with an overall j factor of 2.07 (SD = 0.5). For both indices, context use decreased with increasing hearing loss once the average hearing loss exceeded 55 dB HL. In right-handed patients, significantly greater context influence was observed for words presented in the right ears than for words presented in the left, especially in patients with many years of education. The correlations between raw word scores (and context influence indices) and word occurrence frequencies showed a significant age-dependent effect, with a stronger correlation between perception scores and word occurrence frequencies when the occurrence frequencies were based on the years corresponding to the patients' youth, showing a "historic" word frequency effect. This effect was still observed for patients with few years of formal education, but recent occurrence frequencies based on current word exposure had a stronger influence for those patients, especially for younger ones.

Determination of Rod and Cone Influence to the Early and Late Dynamic of the Pupillary Light Response.

PURPOSE: This study aims to identify which aspects of the pupil light reflex are most influenced by rods and cones independently by analyzing pupil recordings from different mouse models of photoreceptor deficiency. METHODS: One-month-old wild type (WT), rodless (Rho-/-), coneless (Cnga3-/-), or photoreceptor less (Cnga3-/-; Rho-/- or Gnat1-/-) mice were subjected to brief red and blue light stimuli of increasing intensity. To describe the initial dynamic response to light, the maximal pupillary constriction amplitudes and the derivative curve of the first 3 seconds were determined. To estimate the postillumination phase, the constriction amplitude at 9.5 seconds after light termination was related to the maximal constriction amplitude. RESULTS: Rho-/- mice showed decreased constriction amplitude but more prolonged pupilloconstriction to all blue and red light stimuli compared to wild type mice. Cnga3-/- mice had constriction amplitudes similar to WT however following maximal constriction, the early and rapid dilation to low intensity blue light was decreased. To high intensity blue light, the Cnga3-/- mice demonstrated marked prolongation of the pupillary constriction. Cnga3-/-; Rho-/- mice had no pupil response to red light of low and medium intensity. CONCLUSIONS: From specific gene defective mouse models which selectively voided the rod or cone function, we determined that mouse rod photoreceptors are highly contributing to the pupil response to blue light stimuli but also to low and medium red stimuli. We also observed that cone cells mainly drive the partial rapid dilation of the initial response to low blue light stimuli. Thus photoreceptor dysfunction can be derived from chromatic pupillometry in mouse models.

Recognition of prior learning in online postgraduate education

The recognition of prior experiential learning (RPEL) involves the assessment ofskills and knowledge acquired by an individual through previous experience, which isnot necessarily related to an academic context. RPEL practices are far from generalisedin higher education, and there is a lack of specific guidelines on how to implement RPLprograms in particular settings, such as management education or online programs. TheRPEL pilot program developed in a Spanish virtual university is used throughout thearticle as the basis for further reflection on the design and implementation of RPEL inonline postgraduate education in the business field. The role of competences as a centraltheoretical foundation for RPEL is explained, and the context and characteristics of theRPEL program described. Special attention is paid to the key elements of the program¿sdesign and to the practical aspects of its implementation. The results of the program areassessed and general conclusions and suggestions for further research are discussed.

Shared feature extraction for nearest neighbor face recognition

In this paper, we propose a new supervised linearfeature extraction technique for multiclass classification problemsthat is specially suited to the nearest neighbor classifier (NN).The problem of finding the optimal linear projection matrix isdefined as a classification problem and the Adaboost algorithmis used to compute it in an iterative way. This strategy allowsthe introduction of a multitask learning (MTL) criterion in themethod and results in a solution that makes no assumptions aboutthe data distribution and that is specially appropriated to solvethe small sample size problem. The performance of the methodis illustrated by an application to the face recognition problem.The experiments show that the representation obtained followingthe multitask approach improves the classic feature extractionalgorithms when using the NN classifier, especially when we havea few examples from each class

Active regions for colour texture segmentation integrating region and boundary information

In this paper a colour texture segmentation method, which unifies region and boundary information, is proposed. The algorithm uses a coarse detection of the perceptual (colour and texture) edges of the image to adequately place and initialise a set of active regions. Colour texture of regions is modelled by the conjunction of non-parametric techniques of kernel density estimation (which allow to estimate the colour behaviour) and classical co-occurrence matrix based texture features. Therefore, region information is defined and accurate boundary information can be extracted to guide the segmentation process. Regions concurrently compete for the image pixels in order to segment the whole image taking both information sources into account. Furthermore, experimental results are shown which prove the performance of the proposed method