6,676 research outputs found

    Multiprotein DNA looping

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    DNA looping plays a fundamental role in a wide variety of biological processes, providing the backbone for long range interactions on DNA. Here we develop the first model for DNA looping by an arbitrarily large number of proteins and solve it analytically in the case of identical binding. We uncover a switch-like transition between looped and unlooped phases and identify the key parameters that control this transition. Our results establish the basis for the quantitative understanding of fundamental cellular processes like DNA recombination, gene silencing, and telomere maintenance.Comment: 11 pages, 4 figure

    Failure of the work-Hamiltonian connection for free energy calculations

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    Extensions of statistical mechanics are routinely being used to infer free energies from the work performed over single-molecule nonequilibrium trajectories. A key element of this approach is the ubiquitous expression dW/dt=\partial H(x,t)/ \partial t which connects the microscopic work W performed by a time-dependent force on the coordinate x with the corresponding Hamiltonian H(x,t) at time t. Here we show that this connection, as pivotal as it is, cannot be used to estimate free energy changes. We discuss the implications of this result for single-molecule experiments and atomistic molecular simulations and point out possible avenues to overcome these limitations

    Huawei case study : a reposition challenge to achieve leadership

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    Having as a focus the practical dilemma of Huawei’s repositioning strategy in Portugal, the present dissertation places under analysis the efficiency of the brand’s strategy evaluated through the changes in consumers’ perceptions, and therefore, market acquisition. Huawei is a Chinese IT solutions provider since 1987. Placing the client at the center of their activities, the brand aims to offer the best experience to its consumers through their smartphones. Through strategic partnerships with well-known partners, the brand aims to build a better-connected world, acquiring the number one spot as the most preferable and trustworthy brand of its target audience. Nevertheless, Huawei entered the Portuguese market with low-quality equipment, usually the operators private labels, associated to a low performance, trust, and durability. Therefore, the brand still suffers nowadays with the consequences of this association, not be-ing seen by consumers as a trustworthy brand of reference, even with its products being of high performance and quality, a result of the great investment made in R&D. As a response to this market’s perception, the brand went through a repositioning strategy. Thus, it is intended to study, through primary and secondary research, if the repositioning strategy of Huawei managed to change the it market’s perception, and if there was actually an added value to the consumer. The main results demonstrate that the brand’s market perception is under high evolution, hav-ing acquired a favorable opinion with its consumers, which if maintained in the long-term, it will lead to buying intentions.como foco o dilema do reposicionamento da Huawei em Portugal, a presente dissertação coloca sob análise a eficiência da estratégia da marca avaliada através da alteração da percepção dos consumidores e consequente conquista de mercado. A Huawei é uma marca Chinesa, que fornece soluções de Tecnologia integradas desde 1987. Colocando o cliente no centro da sua actividade, a marca procura oferecer a melhor experiência aos seus consumidores através dos seus smartphones. Através de parcerias estratégicas, com parceiros de renome, ambiciona construir um mundo mais conectado e conquistar o lugar de marca preferida e de confiança dos consumidores. No entanto, a Huawei entrou no mercado Português com telemóveis de baixa gama, sendo muitas vezes os equipamentos de marca branca dos operadores reflexo de baixo desempenho, confiança e durabilidade. Consequentemente, a marca sofre ainda hoje com as consequências desta associação, não sendo vista pelos consumidores como uma marca de referencia e confiança apesar dos seus produtos serem actualmente de enorme desempenho e qualidade graças à grande aposta da marca em investigação e desenvolvimento. Em resposta a esta percepção de mercado a marca reposicionou-se. Assim, pretende-se estudar, através de pesquisa primária e secundária, se o reposicionamento estratégico da marca alterou as percepções de mercado sobre a Huawei representando actualmente um valor acrescentado para o consumidor. Os principais resultados mostraram que a percepção da marca está em grande evolução, tendo conquistado uma opinião favorável junto dos consumidores, factor que a manter-se a longo prazo conduzirá a intenções de compra

    Comparison of energy estimates in chronic kidney disease using doubly-labelled water

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    This is the peer reviewed version of the following article: S. Sridharan, J. Wong, E. Vilar, and K. Farrington, ‘Comparison of energy estimates in chronic kidney disease using doubly-labelled water’, Journal of Human Nutrition and Dietetics, Vol. 29 (1): 59-66, February 2016, which has been published in final form at https://doi.org/10.1111/jhn.12326. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. © 2015 The British Dietetic Association Ltd.BACKGROUND: Total energy expenditure (TEE) is estimated in clinical practice as a combined measure of resting energy expenditure and physical activity level. Commonly available questionnaires to estimate physical activity level have not been validated in patients with kidney disease using the doubly-labelled water method. METHODS: This prospective, cross-sectional study was conducted on 40 patients with chronic kidney disease stages 1-5 with the objective of validating two physical activity questionnaires: the Recent Physical Activity Questionnaire (RPAQ) and the Stanford 7-day recall questionnaire. TEE was measured using doubly-labelled water technique. TEE was also estimated using predicted resting energy expenditure and estimated physical activity measures from the questionnaires. RESULTS: Measured TEE correlated better with TEE estimated from RPAQ compared to that from the Stanford questionnaire. In Bland-Altman analysis, TEE estimated from RPAQ had the least bias and narrower limits of agreement compared to the measured TEE. A metabolic equivalent of task value of 1.3 for the unaccounted time in RPAQ provided the best approximation of estimated TEE to the measured TEE. CONCLUSIONS: RPAQ is an acceptable questionnaire tool for assessing physical activity level in patients with chronic kidney disease.Peer reviewedFinal Accepted Versio

    Stochastic Resonance in Noisy Non-Dynamical Systems

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    We have analyzed the effects of the addition of external noise to non-dynamical systems displaying intrinsic noise, and established general conditions under which stochastic resonance appears. The criterion we have found may be applied to a wide class of non-dynamical systems, covering situations of different nature. Some particular examples are discussed in detail.Comment: 4 pages, RevTex, 3 PostScript figures available upon reques

    Digital technologies in architecture and engineering: Exploring an engaged interaction within curricula

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    This chapter focuses on the development and adoption of new Multimedia, Computer Aided Design, and other ICT technologies for both Architecture and Computer Sciences curricula and highlights the multidisciplinary work that can be accomplished when these two areas work together. We describe in detail the addressed educational skills and the developed research and we highlight the contributions towards the improvements of teaching and learning in those areas. We discuss in detail the role of Digital technologies, such as Virtual Reality, Augmented Reality, Multimedia, 3D Modelling software systems, Design Processes and its evaluation tools, such as Shape Grammar and Space Syntax, within the Architecture curricula.info:eu-repo/semantics/acceptedVersio

    Noise and Periodic Modulations in Neural Excitable Media

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    We have analyzed the interplay between noise and periodic modulations in a mean field model of a neural excitable medium. To this purpose, we have considered two types of modulations; namely, variations of the resistance and oscillations of the threshold. In both cases, stochastic resonance is present, irrespective of if the system is monostable or bistable.Comment: 13 pages, RevTex, 5 PostScript figure

    Interview anxiety narrative validation for a virtual reality-based study

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    When conducting a Virtual Reality-based study one important feature that needs to be assured is valid is the narrative context. Our objective was to validate a job interview anxiety provoking narrative. One experiment with a between-subject design was conducted. Participants were instructed to read a job interview-context narrative and then self-report the level of anxiety experienced. Results indicated that the narrative describing the individual’s parents’ economic and financial difficulties as well as an ambiguous description of the organization’s physical characteristics elicited significantly higher levels of state anxiety. Research findings suggests the potential influence the narrative may have on interview anxiety and, most importantly, evidence the validity of instruments necessary for a Virtual Reality-based methodology.info:eu-repo/semantics/publishedVersio

    Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

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    Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035
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