60 research outputs found

    Caso de estudio del uso de las Power Platform en un entorno empresarial: GSK Academy

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    Con este trabajo se ha documentado un caso de estudio del uso Power Plataform en un entorno empresarial específico. La investigación se centra en los beneficios y desafíos del uso de estas herramientas low code para mejorar la eficiencia y la productividad de la empresa. Se analiza el proceso de implementación de las Power Plataform y se describe las soluciones creadas utilizando Power Apps, Power BI y Power Automate. El estudio muestra cómo las Power Plataform pueden ayudar a las empresas a mejorar la gestión de proyectos, a automatizar procesos manuales y a crear soluciones personalizadas adaptadas a sus necesidades especificas. Además, se destacan algunos desafíos y limitaciones, y la integración con otras herramientas empresariales como Sharepoint. Este trabajo demuestra que el uso de las Power Platform puede ser una estrategia efectiva para mejorar la productividad y la eficiencia en las empresas, y que su implantación exitosa depende en gran medida de la comprensión de las necesidades y objetivos específicos de la empresa.Grado en Ingeniería Informátic

    Real-Time Dynamics of RNA Polymerase II Clustering in Live Human Cells

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    Transcription is reported to be spatially compartmentalized in nuclear transcription factories with clusters of RNA polymerase II (Pol II). However, little is known about when these foci assemble or their relative stability. We developed a quantitative single-cell approach to characterize protein spatiotemporal organization, with single-molecule sensitivity in live eukaryotic cells. We observed that Pol II clusters form transiently, with an average lifetime of 5.1 (± 0.4) seconds, which refutes the notion that they are statically assembled substructures. Stimuli affecting transcription yielded orders-of-magnitude changes in the dynamics of Pol II clusters, which implies that clustering is regulated and plays a role in the cell’s ability to effect rapid response to external signals. Our results suggest that transient crowding of enzymes may aid in rate-limiting steps of gene regulation

    Tuberculosis active case finding in Cambodia: a pragmatic, cost-effectiveness comparison of three implementation models.

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    BACKGROUND: Globally, almost 40% of tuberculosis (TB) patients remain undiagnosed, and those that are diagnosed often experience prolonged delays before initiating correct treatment, leading to ongoing transmission. While there is a push for active case finding (ACF) to improve early detection and treatment of TB, there is extremely limited evidence about the relative cost-effectiveness of different ACF implementation models. Cambodia presents a unique opportunity for addressing this gap in evidence as ACF has been implemented using different models, but no comparisons have been conducted. The objective of our study is to contribute to knowledge and methodology on comparing cost-effectiveness of alternative ACF implementation models from the health service perspective, using programmatic data, in order to inform national policy and practice. METHODS: We retrospectively compared three distinct ACF implementation models - door to door symptom screening in urban slums, checking contacts of TB patients, and door to door symptom screening focusing on rural populations aged above 55 - in terms of the number of new bacteriologically-positive pulmonary TB cases diagnosed and the cost of implementation assuming activities are conducted by the national TB program of Cambodia. We calculated the cost per additional case detected using the alternative ACF models. RESULTS: Our analysis, which is the first of its kind for TB, revealed that the ACF model based on door to door screening in poor urban areas of Phnom Penh was the most cost-effective (249 USD per case detected, 737 cases diagnosed), followed by the model based on testing contacts of TB patients (308 USD per case detected, 807 cases diagnosed), and symptomatic screening of older rural populations (316 USD per case detected, 397 cases diagnosed). CONCLUSIONS: Our study provides new evidence on the relative effectiveness and economics of three implementation models for enhanced TB case finding, in line with calls for data from 'routine conditions' to be included in disease control program strategic planning. Such cost-effectiveness comparisons are essential to inform resource allocation decisions of national policy makers in resource constraint settings. We applied a novel, pragmatic methodological approach, which was designed to provide results that are directly relevant to policy makers, costing the interventions from Cambodia's national TB program's perspective and using case finding data from implementation activities, rather than experimental settings

    Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus

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    Gene regulation relies on transcription factors (TFs) exploring the nucleus searching their targets. So far, most studies have focused on how fast TFs diffuse, underestimating the role of nuclear architecture. We implemented a single-molecule tracking assay to determine TFs dynamics. We found that c-Myc is a global explorer of the nucleus. In contrast, the positive transcription elongation factor P-TEFb is a local explorer that oversamples its environment. Consequently, each c-Myc molecule is equally available for all nuclear sites while P-TEFb reaches its targets in a position-dependent manner. Our observations are consistent with a model in which the exploration geometry of TFs is restrained by their interactions with nuclear structures and not by exclusion. The geometry-controlled kinetics of TFs target-search illustrates the influence of nuclear architecture on gene regulation, and has strong implications on how proteins react in the nucleus and how their function can be regulated in space and time.Nikon France (Research contract)France. Agence nationale de la recherche (PCV DYNAFT 08-PCVI-0013)France. Agence nationale de la recherche (DynamIC ANR-12-BSV5-0018)Fondation pour la recherche médicaleNetherlands Organization for Scientific Research (Rubicon fellowship

    Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus

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    Gene regulation relies on transcription factors (TFs) exploring the nucleus searching their targets. So far, most studies have focused on how fast TFs diffuse, underestimating the role of nuclear architecture. We implemented a single-molecule tracking assay to determine TFs dynamics. We found that c-Myc is a global explorer of the nucleus. In contrast, the positive transcription elongation factor P-TEFb is a local explorer that oversamples its environment. Consequently, each c-Myc molecule is equally available for all nuclear sites while P-TEFb reaches its targets in a position-dependent manner. Our observations are consistent with a model in which the exploration geometry of TFs is restrained by their interactions with nuclear structures and not by exclusion. The geometry-controlled kinetics of TFs target-search illustrates the influence of nuclear architecture on gene regulation, and has strong implications on how proteins react in the nucleus and how their function can be regulated in space and time

    Nuclear target search at the single molecule level: protein interactions define the exploration landscape

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    Gene regulation relies on highly mobile transcription factors (TFs) exploring the nucleoplasm in search of their targets. Our view of the nucleus has evolved from that of an isotropic and homogenous reactor to that of a highly organized yet very dynamic organelle. However important questions remain on how these regulatory factors explore the nuclear environment in search of their DNA or protein targets, and how their exploration strategy affects the kinetics of transcriptional regulation. We implemented a single-molecule tracking assay to determine the TFs dynamics using photoactivatable tags in human cells. We investigated the mobility of several nuclear proteins, including the transcription factor c-Myc and the elongation factor P-TEFb. We found that, while their diffusion speed was comparable, these proteins largely differed in terms of their exploration geometry. We discovered that c-Myc is a global explorer diffusing in the nucleus without spatial constraints. In contrast, the positive transcription elongation factor P-TEFb is a local explorer that oversamples its environment, constrained by a fractal nuclear architecture. Consequently, each c-Myc molecule is equally available for all nuclear sites while P-TEFb reaches its targets in a position-dependent manner. We also measured the mobility of a P-TEFb mutant in which the interaction with the CTD of the RNA Pol II was truncated. In this case, the single-molecule experiments suggested a global exploration of the P-TEFb mutant, consistent with free diffusion. Our observations are in line with a model in which the exploration geometry of TFs is constrained by their interactions and not by exclusion properties. Our findings have strong implications on how proteins react in the nucleus and how their function can be regulated in space and time
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