910 resultados para Cis-acting Elements
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Aquest article presenta una breu anàlisi de la situació actual de l’Educació Secundària, centrada en vuit punts: els continguts curriculars, els mètodes d’ensenyament-aprenentatge, la motivació de l’alumnat, la motivació del professorat, l’avaluació, la tutoria de grup, la tutoria individual i les relacions escola-família. Com a pistes de futur assenyala cinc aspectes: els espais de trobada escola-família, concretar els valors i conviccions de pares i mestres, l’actuació dels equips interdisciplinaris, la valoració multidimensional del progrés dels alumnes i el rellançament de la tutoria.
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La docencia no presencial permite ahorro de tiempo y de desplazamientos para los alumnos, de manera que contribuye a disminuir el coste de la docencia.
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This paper presents the use of our multimodal mixed reality telecommunication system to support remote acting rehearsal. The rehearsals involved two actors, located in London and Barcelona, and a director in another location in London. This triadic audiovisual telecommunication was performed in a spatial and multimodal collaborative mixed reality environment based on the 'destination-visitor' paradigm, which we define and put into use. We detail our heterogeneous system architecture, which spans the three distributed and technologically asymmetric sites, and features a range of capture, display, and transmission technologies. The actors' and director's experience of rehearsing a scene via the system are then discussed, exploring successes and failures of this heterogeneous form of telecollaboration. Overall, the common spatial frame of reference presented by the system to all parties was highly conducive to theatrical acting and directing, allowing blocking, gross gesture, and unambiguous instruction to be issued. The relative inexpressivity of the actors' embodiments was identified as the central limitation of the telecommunication, meaning that moments relying on performing and reacting to consequential facial expression and subtle gesture were less successful.
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While there is evidence that the two ubiquitously expressed thyroid hormone (T3) receptors, TRalpha1 and TRbeta1, have distinct functional specificities, the mechanism by which they discriminate potential target genes remains largely unexplained. In this study, we demonstrate that the thyroid hormone response elements (TRE) from the malic enzyme and myelin basic protein genes (METRE and MBPTRE) respectively, are not functionally equivalent. The METRE, which is a direct repeat motif with a 4-base pair gap between the two half-site hexamers binds thyroid hormone receptor as a heterodimer with 9-cis-retinoic acid receptor (RXR) and mediates a high T3-dependent activation in response to TRalpha1 or TRbeta1 in NIH3T3 cells. In contrast, the MBPTRE, which consists of an inverted palindrome formed by two hexamers spaced by 6 base pairs, confers an efficient transactivation by TRbeta1 but a poor transactivation by TRalpha1. While both receptors form heterodimers with RXR on MBPTRE, the poor transactivation by TRalpha1 correlates also with its ability to bind efficiently as a monomer. This monomer, which is only observed with TRalpha1 bound to MBPTRE, interacts neither with N-CoR nor with SRC-1, explaining its functional inefficacy. However, in Xenopus oocytes, in which RXR proteins are not detectable, the transactivation mediated by TRalpha1 and TRbeta1 is equivalent and independent of a RXR supply, raising the question of the identity of the thyroid hormone receptor partner in these cells. Thus, in mammalian cells, the binding characteristics of TRalpha1 to MBPTRE (i.e. high monomer binding efficiency and low transactivation activity) might explain the particular pattern of T3 responsiveness of MBP gene expression during central nervous system development.
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In eukaryotic cells, transgene expression levels may be limited by an unfavourable chromatin structure at the integration site. Epigenetic regulators are DNA sequences which may protect transgenes from such position effect. We evaluated different epigenetic regulators for their ability to protect transgene expression at telomeres, which are commonly associated to low or inconsistent expression because of their repressive chromatin environment. Although to variable extents, matrix attachment regions (MARs), ubiquitous chromatin opening element (UCOE) and the chicken cHS4 insulator acted as barrier elements, protecting a telomeric-distal transgene from silencing. MARs also increased the probability of silent gene reactivation in time-course experiments. Additionally, all MARs improved the level of expression in non-silenced cells, unlike other elements. MARs were associated to histone marks usually linked to actively expressed genes, especially acetylation of histone H3 and H4, suggesting that they may prevent the spread of silencing chromatin by imposing acetylation marks on nearby nucleosomes. Alternatively, an UCOE was found to act by preventing deposition of repressive chromatin marks. We conclude that epigenetic DNA elements used to enhance and stabilize transgene expression all have specific epigenetic signature that might be at the basis of their mode of action.
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Peer-reviewed
Resumo:
This paper presents the use of our multimodal mixed reality telecommunication system to support remote acting rehearsal. The rehearsals involved two actors, located in London and Barcelona, and a director in another location in London. This triadic audiovisual telecommunication was performed in a spatial and multimodal collaborative mixed reality environment based on the 'destination-visitor' paradigm, which we define and put into use. We detail our heterogeneous system architecture, which spans the three distributed and technologically asymmetric sites, and features a range of capture, display, and transmission technologies. The actors' and director's experience of rehearsing a scene via the system are then discussed, exploring successes and failures of this heterogeneous form of telecollaboration. Overall, the common spatial frame of reference presented by the system to all parties was highly conducive to theatrical acting and directing, allowing blocking, gross gesture, and unambiguous instruction to be issued. The relative inexpressivity of the actors' embodiments was identified as the central limitation of the telecommunication, meaning that moments relying on performing and reacting to consequential facial expression and subtle gesture were less successful.
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We present a complete Raman spectroscopic study in two structurally well-defined diradical species of different lengths incorporating oligo p-phenylene vinylene bridges between two polychlorinated triphenylmethyl radical units, a disposition that allows sizeable conjugation between the two radicals through and with the bridge. The spectroscopic data are interpreted and supported by quantum chemical calculations. We focus the attention on the Raman frequency changes, interpretable in terms of: (i) bridge length (conjugation length); (ii) bridge conformational structure; and (iii) electronic coupling between the terminal radical units with the bridge and through the bridge, which could delineate through-bond spin polarization, or spin delocalization. These items are addressed by using the"oligomer approach" in conjunction with pressure and temperature dependent Raman spectroscopic data. In summary, we have attempted to translate the well-known strategy to study the electron (charge) structure of π−conjugated molecules by Raman spectroscopy to the case of electron (spin) interactions via the spin delocalization mechanism.
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Purpose: To describe (1) the clinical profiles and the patterns of use of long-acting injectable (LAI) antipsychotics in patients with schizophrenia at risk of nonadherence with oral antipsychotics, and in those who started treatment with LAI antipsychotics, (2) health care resource utilization and associated costs. Patients and methods: A total of 597 outpatients with schizophrenia at risk of nonadherence, according to the psychiatrist's clinical judgment, were recruited at 59 centers in a noninterventional prospective observational study of 1-year follow-up when their treatment was modified. In a post hoc analysis, the profiles of patients starting LAI or continuing with oral antipsychotics were described, and descriptive analyses of treatments, health resource utilization, and direct costs were performed in those who started an LAI antipsychotic. Results: Therapy modifications involved the antipsychotic medications in 84.8% of patients, mostly because of insufficient efficacy of prior regimen. Ninety-two (15.4%) patients started an LAI antipsychotic at recruitment. Of these, only 13 (14.1%) were prescribed with first-generation antipsychotics. During 1 year, 16.3% of patients who started and 14.9% of patients who did not start an LAI antipsychotic at recruitment relapsed, contrasting with the 20.9% who had been hospitalized only within the prior 6 months. After 1 year, 74.3% of patients who started an LAI antipsychotic continued concomitant treatment with oral antipsychotics. The mean (median) total direct health care cost per patient per month during the study year among the patients starting any LAI antipsychotic at baseline was 1,407 ( 897.7). Medication costs (including oral and LAI antipsychotics and concomitant medication) represented almost 44%, whereas nonmedication costs accounted for more than 55% of the mean total direct health care costs. Conclusion: LAI antipsychotics were infrequently prescribed in spite of a psychiatrist-perceived risk of nonadherence to oral antipsychotics. Mean medication costs were lower than nonmedication costs.
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Eurooppalaisia ja suomalaisia markkinavalvontatilastoja tutkimalla havaitaan, ettei tuoteturvallisuuden hallinta ole itsestään selvää sähkö- ja elektroniikka-alalla. Vuodesta 2000 maaliskuuhun 2006Euroopan markkinoilla havaittiin 3040 vaarallista kuluttajien käyttöön tarkoitettua sähkötuotetta. Työn päätavoitteena on selvittää, miten tuoteturvallisuusriskien hallinta kytkeytyy yrityksen suorituskyvyn johtamiseen. Työssä on käytetty konstruktiivista tutkimusotetta. Aineistopohjaisen analyysin avulla kartoitetaan suorituskyvyn johtamisen teoriaa, suorituskyvyn käytännön mittaamista pienissä ja keskisuurissa yrityksissä sekä tuoteturvallisuusriskejä jariskienhallinnan periaatteita. Lisäksi kartoitetaan lainsäädännön vaatimuksia, tuotesuunnittelua, valmistusta ja osaamista sekä tarkastellaan tuoteturvallisuuden viranomaisvalvonnan tuloksia. Tutkimuksessa analysoidaan kirjallisuutta ja tilastoja etsien tuoteriskien hallinnan ja suorituskyvyn johtamisen välistä yhteyttä. Analyysiä täydennetään tutkimuksen tekijän kokemuksella tuoteturvallisuuden testauksesta ja sertifioinnista, standardisoimistyöstä sekä tuoteturvallisuuden viranomaisvalvonnasta. Riskienhallinta muodostaa parhaimmillaan osan yrityksen johtamis- ja hallintakäytäntöä. Tuoteturvallisuusriskien hallinta on yrityksen strateginen päätös, joka tukee suorituskyvyn johtamista. Työssämallinnetaan kolme toimintatapaa, joilla eri kehitysvaiheessa olevat sähkö- ja elektroniikkateollisuuden valmistajat voivat hallita tuoteturvallisuusriskejään.Työssä kootaan yhteen tuoteturvallisuuden tekijöitä, jotka suorituskyvyn mittareissa monitoroivat tuoteriskien tilaa. Lisäksi kootaan yhteen riskienhallinnan kustannuksia, joilla yritys voi arvioida etukäteen kokonaiskustannuksia.
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RPE65 is a retinoid isomerase required for the production of 11-cis-retinal, the chromophore of both cone and rod visual pigments. We recently established an R91W knock-in mouse strain as homologous animal model for patients afflicted by this mutation in RPE65. These mice have impaired vision and can only synthesize minute amounts of 11-cis-retinal. Here, we investigated the consequences of this chromophore insufficiency on cone function and pathophysiology. We found that the R91W mutation caused cone opsin mislocalization and progressive geographic cone atrophy. Remnant visual function was mostly mediated by rods. Ablation of rod opsin corrected the localization of cone opsin and improved cone retinal function. Thus, our analyses indicate that under conditions of limited chromophore supply rods and cones compete for 11-cis-retinal that derives from regeneration pathway(s) which are reliant on RPE65. Due to their higher number and the instability of cone opsin, rods are privileged under this condition while cones suffer chromophore deficiency and degenerate. These findings reinforce the notion that in patients any effective gene therapy with RPE65 needs to target the cone-rich macula directly to locally restore the cones' chromophore supply outside the reach of rods.
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El present document es centra en un dels edificis més emblemàtics i de més valor patrimonial de la ciutat de Tortosa, la Catedral de Santa Maria, i dintre d'aquest, en la capçalera de la nau central, l'absis, tot durant la seva construcció entre els segles XIV i XV. L'objectiu principal és aconseguir un recull suficient de dades que expliquin diverses idees d'autors, arquitectes, enginyers, etc. que tractin aquests temes, i extraure al final, una idea general que ens permeti realitzar una hipòtesi sobre la metodologia constructiva aplicada, i sobre els elements auxiliars que es van utilitzar en aquell moment.
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This paper asks a simple question: if humans and their actions co-evolve with hydrological systems (Sivapalan et al., 2012), what is the role of hydrological scientists, who are also humans, within this system? To put it more directly, as traditionally there is a supposed separation of scientists and society, can we maintain this separation as socio-hydrologists studying a socio-hydrological world? This paper argues that we cannot, using four linked sections. The first section draws directly upon the concern of science-technology studies to make a case to the (socio-hydrological) community that we need to be sensitive to constructivist accounts of science in general and socio-hydrology in particular. I review three positions taken by such accounts and apply them to hydrological science, supported with specific examples: (a) the ways in which scientific activities frame socio-hydrological research, such that at least some of the knowledge that we obtain is constructed by precisely what we do; (b) the need to attend to how socio-hydrological knowledge is used in decision-making, as evidence suggests that hydrological knowledge does not flow simply from science into policy; and (c) the observation that those who do not normally label themselves as socio-hydrologists may actually have a profound knowledge of socio-hydrology. The second section provides an empirical basis for considering these three issues by detailing the history of the practice of roughness parameterisation, using parameters like Manning's n, in hydrological and hydraulic models for flood inundation mapping. This history sustains the third section that is a more general consideration of one type of socio-hydrological practice: predictive modelling. I show that as part of a socio-hydrological analysis, hydrological prediction needs to be thought through much more carefully: not only because hydrological prediction exists to help inform decisions that are made about water management; but also because those predictions contain assumptions, the predictions are only correct in so far as those assumptions hold, and for those assumptions to hold, the socio-hydrological system (i.e. the world) has to be shaped so as to include them. Here, I add to the ``normal'' view that ideally our models should represent the world around us, to argue that for our models (and hence our predictions) to be valid, we have to make the world look like our models. Decisions over how the world is modelled may transform the world as much as they represent the world. Thus, socio-hydrological modelling has to become a socially accountable process such that the world is transformed, through the implications of modelling, in a fair and just manner. This leads into the final section of the paper where I consider how socio-hydrological research may be made more socially accountable, in a way that is both sensitive to the constructivist critique (Sect. 1), but which retains the contribution that hydrologists might make to socio-hydrological studies. This includes (1) working with conflict and controversy in hydrological science, rather than trying to eliminate them; (2) using hydrological events to avoid becoming locked into our own frames of explanation and prediction; (3) being empirical and experimental but in a socio-hydrological sense; and (4) co-producing socio-hydrological predictions. I will show how this might be done through a project that specifically developed predictive models for making interventions in river catchments to increase high river flow attenuation. Therein, I found myself becoming detached from my normal disciplinary networks and attached to the co-production of a predictive hydrological model with communities normally excluded from the practice of hydrological science.