Cis-configured aziridines are new pseudo-irreversible dual-mode inhibitors of Candida albicans secreted aspartic protease 2

A series of cis-configured epoxides and aziridines containing hydrophobic moieties and amino acid esters,were synthesized as new potential inhibitors of the secreted aspartic protease 2 (SAP2) of Candida albicans. Enzyme assays revealed the N- benzyl-3-phenyl-substituted aziridines 11 and 17 as the most potent inhibitors, with second-order inhibition, rate constants (k(2)) between 56000 and 12-1000 M-1 min(-1). The compounds were shown to be pseudo-irreversible dual-mode, inhibitors: the interm ediate esterified enzyme resulting from nucleophilic ring opening was hydrolyzed and yielded amino alcohols as transition state-mimetic reversible inhibitors. The results of docking studies with the ring-closed aziridine forms of the inhibitors suggest binding modes mainly dominated by hydrophobic interactions with the S1, S1' S2, and S2' subsites of the protease, and docking studies with the processed amino alcohol forms predict additional hydrogen bonds of the new hydroxy group to the active site Asp residues. C. albicans growth assays showed the compounds to decrease SAP2-dependent growth while not affecting SAP2-independent growth.

Limitations of stimulated echo acquisition mode (STEAM) techniques in cardiac applications.

Stimulated echoes are widely used for imaging functional tissue parameters such as diffusion coefficient, perfusion, and flow rates. They are potentially interesting for the assessment of various cardiac functions. However, severe limitations of the stimulated echo acquisition mode occur, which are related to the special dynamic properties of the beating heart and flowing blood. To the well-known signal decay due to longitudinal relaxation and through-plane motion between the preparation and the read-out period of the stimulated echoes, additional signal loss is often observed. As the prepared magnetization is fixed with respect to the tissue, this signal loss is caused by the tissue deformation during the cardiac cycle, which leads to a modification of the modulation frequency of the magnetization. These effects are theoretically derived and corroborated by phantom and in vivo experiments.

Energy investment in gynes of the Argentine ant Iridomyrmex humilis (Mayr) in relation to the mode of colony founding in ants (Hymenoptera, Formicidae)

The increase in weight, fat and energy content of queens was studied in Iridomyrmex humilis (Mayr) in relation to the mode of colony founding in ants. The increase in energy content of gynes during the time between emergence and mating reaches only 80% in this species in which queens found colonies with the help of workers (dependent mode), whereas it can reach 470% in species in which queens found colonies without the help of workers (independent mode). These results are discussed with regard to the investment in energy required by each mode of colony founding.

IDENTITÉ, PROJET, CHANGEMENT : DES REPRÉSENTATIONS SOCIALES AUX LEVIERS DE L'ACTION PUBLIQUE. POUR UN MODE DE GOUVERNANCE AXÉ SUR LE DÉVELOPPEMENT TERRITORIAL. ETUDE DE CAS : CANTON DU JURA (SUISSE)

Thirty years after the Canton of Jura entered sovereignty, it has to be admited that the creation of the newly canton did't fullfill the hopes of economic and demografic growth that many could have expected from political independance. Through a plurality of complementary approaches, the research suggest a closer look at, on one hand, the position of the Canton in its territorial context as well as its structure and dynamics and on the other hand, the representations of the territory and its evolution by the social actors. This in order to formulate a set of social demands (of debate, of openness and of overcoming cleavages) which augurs for a new territoriality regime and testify of a requirement of reflexivity toward the state institutions and actions. The analysis allowed to set in evidence the central role of the couple identity-project in the dynamics of change, and to identifiy three main periods in the recent past of the Canton: a period of territorialization, during which grew a strong collective identity, coupled with a major project of society (the creation of the canton of Jura); then followed a period of deterritorialization, with the fragmentation of the collective identity and the lack of a project of society. Then, the third period, with a paradoxical event, the failure in public vote of the the project Jura open Land (Jura Pays ouvert), which was meant to give a second wind to the Canton. We consider this turning point as the start of a new period (of reterritorialization), with an issue linked with the outlines of a renewed "jurassian" identity and the elaboration of a shared territory project.Trente ans après l'entrée en souveraineté, force est de constater que la création du canton du Jura n'a pas permis de répondre aux espérances de développement économique et démographique que l'indépendance politique devait entraîner dans son sillage. Cette recherche se propose, à travers une pluralité d'approches complémentaires, d'examiner d'une part la position du Canton dans son contexte territorial ainsi que sa structure et sa dynamique; d'autre part, les représentations que se font les acteurs du territoire et de son évolution, pour déboucher sur une série de demandes sociales (de débat, d'ouverture et de dépassement des clivages) qui augurent de la transition vers un nouveau régime de territorialité et témoignent d'une exigence de réflexivité envers les institutions et les actions de l'Etat. L'analyse a permis de mettre en évidence le rôle central du couple identité-projet dans la dynamique de changement et d'identifier trois temps forts dans l'évolution récente du Canton, une phase de territorialisation au cours de laquelle s'est constituée une identité forte doublée d'un projet de société majeur, suivie d'une phase de déterritorialisation avec une fragmentation de l'identité collective et l'absence de projet mobilisateur. Enfin, un moment paradoxal, l'échec du projet Jura Pays ouvert, censé redonner un second souffle au Canton, qui amorce une nouvelle étape (de reterritorialisation) avec un questionnement lié aux contours d'une identité jurassienne renouvelée et à l'élaboration d'un projet de territoire partagé.Les ressorts de la production du territoire et de son développement sont analysés à travers le rôle des représentations sociales dans la constitution identitaire et le projet territorial, à l'exemple du canton du Jura. La mise en évidence du rôle central du couple identité-projet dans la dynamique de changement a permis d'identifier trois temps forts dans l'évolution récente du Canton. Une première phase (la création du canton du Jura), au cours de laquelle s'est constituée une identité forte doublée d'un projet de société majeur, suivie d'une phase au cours de laquelle l'identité collective s'est fragmentée en l'absence de projet mobilisateur (la phase de « gestion » de l'Etat). Puis un moment de rupture (l'échec du projet Jura Pays ouvert) et l'amorce d'une transition vers une nouvelle étape, avec un questionnement lié aux contours d'une identité jurassienne renouvelée, à l'élaboration d'un projet de territoire partagé, et à l'action des pouvoirs publics dans un contexte de repositionnement du Canton.

EEG alpha activity reflects motor preparation rather than the mode of action selection

Alpha-band activity (8-13 Hz) is not only suppressed by sensory stimulation and movements, but also modulated by attention, working memory and mental tasks, and could be sensitive to higher motor control functions. The aim of the present study was to examine alpha oscillatory activity during the preparation of simple left or right finger movements, contrasting the external and internal mode of action selection. Three preparation conditions were examined using a precueing paradigm with S1 as the preparatory and S2 as the imperative cue: Full, laterality instructed by S1; Free, laterality freely selected and None, laterality instructed by S2. Time-frequency (TF) analysis was performed in the alpha frequency range during the S1-S2 interval, and alpha motor-related amplitude asymmetries (MRAA) were also calculated. The significant MRAA during the Full and Free conditions indicated effective external and internal motor response preparation. In the absence of specific motor preparation (None), a posterior alpha event-related desynchronization (ERD) dominated, reflecting the main engagement of attentional resources. In Full and Free motor preparation, posterior alpha ERD was accompanied by a midparietal alpha event-related synchronization (ERS), suggesting a concomitant inhibition of task-irrelevant visual activity. In both Full and Free motor preparation, analysis of alpha power according to MRAA amplitude revealed two types of functional activation patterns: (1) a motor alpha pattern, with predominantly midparietal alpha ERS and large MRAA corresponding to lateralized motor activation/visual inhibition and (2) an attentional alpha pattern, with dominating right posterior alpha ERD and small MRAA reflecting visuospatial attention. The present results suggest that alpha oscillatory patterns do not resolve the selection mode of action, but rather distinguish separate functional strategies of motor preparation.

Comme une mode urbaine : projets de régénération urbaine et patrimonialisation à Porto et Marseille

Partant de deux études de cas, le projet de Frente Ribeirinha à Porto (Portugal) et celui d'Euroméditerranée à Marseille, ce projet de thèse a pour objectif l'étude des modalités de valorisation du tissu bâti (patrimonialisation) par les acteurs institutionnels dans les projets de régénération urbaine. Suivant l'hypothèse de l'entrée dans un nouveau régime de patrimonialité, l'analyse doit expliciter les stratégies à l'oeuvre ainsi que la manière dont les autorités publiques influent sur les représentations de l'espace construit. Abordant la question des échelles d'intervention des projets de régénération urbaine à partir des deux études de cas, mais également de littératures sur des projets anglo-saxons, la thèse cherche à voir, au prisme de la construction patrimoniale, comment ces projets sont directement connectés à l'économie internationale et au phénomène de globalisation et s'ils prennent en compte l'échelle du quotidien et de la domesticité. Il s'agit de montrer les limites d'une valorisation du tissu bâti dans un objectif de retombées économiques (ville consommable) au détriment des valeurs d'usage et de signifiants du quotidien. D'où l'hypothèse de l'importance d'une prise en compte des représentations de valeurs aux différentes échelles (dimensions socio-culturelles du projet de régénération) pour un équilibre qualitatif dans la fabrication du territoire et des projets sur le long terme. La volonté est sensiblement la compréhension des nouvelles constructions patrimoniales ainsi que des pratiques de conception et de mise en oeuvre du projet urbain. - Based on two case studies, the Frente Ribeirinha project in Porto (Portugal) and Euroméditerranée in Marseille, this research project aims at studying the modes of enhancement of the built fabric by institutional actors in urban regeneration projects. Posing the idea of a new heritage regime, this analysis attempts to explain the different strategies at work and how public authorities influence the built space's representations. Looking at the different scales of intervention of regeneration projects in our two case studies, as well as Anglo-Saxon literature on projects, it seeks at seeing, through heritage processes, how these projects are directly connected to the international economy and the phenomenon of globalization. Also, it aims at investigating whether policies take into account the scale of everyday life and domesticity. It attempts to show the limit of a built fabric's valuation with economic benefits objectives (consumable city) rather than taking into account values and meanings of everyday life. Hence, the thesis suggests taking into account representations and values at different scales (socio-cultural dimensions of the regeneration project) for a qualitative balance in urban planning and urban projects' manufacturing. The aim is to broaden the understanding on heritage construction, on urban design practices and on implementation of urban projects.

Stimulated-echo acquisition mode (STEAM) MRI for black-blood delayed hyperenhanced myocardial imaging.

PURPOSE: To develop a breathhold method for black-blood viability imaging of the heart that may facilitate identifying the endocardial border. MATERIALS AND METHODS: Three stimulated-echo acquisition mode (STEAM) images were obtained almost simultaneously during the same acquisition using three different demodulation values. Two of the three images were used to construct a black-blood image of the heart. The third image was a T(1)-weighted viability image that enabled detection of hyperintense infarcted myocardium after contrast agent administration. The three STEAM images were combined into one composite black-blood viability image of the heart. The composite STEAM images were compared to conventional inversion-recovery (IR) delayed hyperenhanced (DHE) images in nine human subjects studied on a 3T MRI scanner. RESULTS: STEAM images showed black-blood characteristics and a significant improvement in the blood-infarct signal-difference to noise ratio (SDNR) when compared to the IR-DHE images (34 +/- 4.1 vs. 10 +/- 2.9, mean +/- standard deviation (SD), P < 0.002). There was sufficient myocardium-infarct SDNR in the STEAM images to accurately delineate infarcted regions. The extracted infarcts demonstrated good agreement with the IR-DHE images. CONCLUSION: The STEAM black-blood property allows for better delineation of the blood-infarct border, which would enhance the fast and accurate measurement of infarct size.

Composition and growth mode of MoSx sputtered films

MoS(x) lubricating thin films were deposited by nonreactive, reactive, and low energy ion-assisted radio-frequency (rf) magnetron sputtering from a MoS2 target. Depending on the total and reactive gas pressures, the film composition ranges between MoS0.7 and MoS2.8. A low working pressure was found to have effects similar to those of low-energy ion irradiation. Films deposited at high pressure have (002) planes preferentially perpendicular to the substrate, whereas films deposited at low pressure or under low-energy ion irradiation have (002) mainly parallel to it. Parallel films are sulfur deficient (MoS1.2-1.4). Their growth is explained in terms of an increased reactivity of the basal surfaces, itself a consequence of the creation of surface defects due to ion irradiation. The films exhibit a lubricating character for all compositions above MoS1.2. The longest lifetime in ball-on-disk wear test was found for MoS1.5.

Effect of physical activity during pregnancy on mode of delivery.

OBJECTIVE: The purpose of this study was to evaluate the effect of structured physical exercise programs during pregnancy on the course of labor and delivery. STUDY DESIGN: We conducted a systematic review and metaanalysis using the following data sources: Medline and The Cochrane Library. In our study, we used randomized controlled trials (RCT) that evaluated the effects of exercise programs during pregnancy on labor and delivery. The results are summarized as relative risks. RESULTS: In the 16 RCTs that were included there were 3359 women. Women in exercise groups had a significantly lower risk of cesarean delivery (relative risk, 0.85; 95% confidence interval [CI], 0.73-0.99). Birthweight was not significantly reduced in exercise groups. The risk of instrumental delivery was similar among groups (relative risk, 1.00; 95% CI, 0.82-1.22). Data on Apgar score, episiotomy, epidural anesthesia, perineal tear, length of labor, and induction of labor were insufficient to draw conclusions. With the use of data from 11 studies (1668 women), our analysis showed that women in the exercise groups gained significantly less weight than women in control groups (mean difference, -1.13 kg; 95% CI, -1.49 to -0.78). CONCLUSION: Structured physical exercise during pregnancy reduces the risk of cesarean delivery. This is an important finding to convince women to be active during their pregnancy and should lead the physician to recommend physical exercise to pregnant women, when this is not contraindicated.

Correction of through-plane deformation artifacts in stimulated echo acquisition mode cardiac imaging.

Attempts to use a stimulated echo acquisition mode (STEAM) in cardiac imaging are impeded by imaging artifacts that result in signal attenuation and nulling of the cardiac tissue. In this work, we present a method to reduce this artifact by acquiring two sets of stimulated echo images with two different demodulations. The resulting two images are combined to recover the signal loss and weighted to compensate for possible deformation-dependent intensity variation. Numerical simulations were used to validate the theory. Also, the proposed correction method was applied to in vivo imaging of normal volunteers (n = 6) and animal models with induced infarction (n = 3). The results show the ability of the method to recover the lost myocardial signal and generate artifact-free black-blood cardiac images.