1,155 research outputs found
The cereblon E3 ligase modulator, CC-90009, rescues CFTR nonsense variants by promoting NMD suppression and PTC readthrough in rectal organoids
No full textApproximately 10% of the worldwide cystic fibrosis (CF) population has premature termination codon (PTC) variants, that prevent translation of cystic fibrosis transmembrane conductance regulator (CFTR) full-length protein and trigger nonsense-mediated mRNA decay (NMD). CFTR modulators approval opened a new era for CF precision medicine, but to date no therapies are still available to restore PTC variants. Readthrough agents that target distinct components of the translation machinery represent a promising and feasible treatment strategy. Analysis of primary cells representative of different variants and patients is necessary to evaluate and compare their effectiveness for a potential clinical evaluation in CF.
Here we investigate the efficacy of the cereblon (CRBN) E3 ubiquitin ligase modulator, CC-90009, in restoring CFTR function and expression using patient-derived rectalorganoids homozygous for W1282X and G542X variants.
Drugs testing were performed on 3D model by Forskolin Induced Swelling (FIS) assay and analysed with an in-house developed AI-based software (SOFTD). CFTR mRNA expression was characterized in response to all compounds by quantitative PCR.
Our data show that CC-90009, as stand alone, induces significant increase of FIS rates compared to vehicle in our cultures, comparable to Vx809-Vx770-treated F508del/F508del carrying organoids. Combination with the aminoglycosides G418 or ELX-02 significantly enhances their mutual effects, dramatically increasing the PTC readthrough response. Furthermore, the mRNA level is incremented by CC-90009 treatment and correlates with functional recovery.
Our results demonstrate that the eRF3a degrader, CC-90009, alone or in combination with other compounds, could represent a promising therapeutic approach to rescue CFTR nonsense variants
State estimation in active distribution networks using convex optimization
No full textActive distribution networks present high penetration of distributed resources that require real-time monitoring. These networks are equipped with a supervision, control, and data acquisition (SCADA) system, which integrates information supplied by advanced measurement equipment. This thesis presents a state estimation model as an integral part of the SCADA system. Nevertheless, the state estimator is non-convex. Therefore, the application of conical approximations such as second-order cone and semidefinite programming proposes to guarantee a global optimum and uniqueness of the solution. The model includes direct angle measurement through meters and micro-phasor measurement units micro-pmu.The model evaluates different test systems in the international scientific literature. These quantified by stochastic metrics the difference between the estimated and actual value as root mean square error or the confidence level used to check for incorrect data and system reliability. In addition, the behavior of the micro-pmu investigates with total voltage error. These results show a high efficiency guaranteeing a global optimum and precision when using cvxPy in Python.Las redes de distribución activas presentan alta penetración de recursos distribuidos que requieren supervisión en tiempo real. Estas redes están equipadas con un sistema supervisión, control y adquisición de datos (SCADA), que integra información suministrada por los equipos de medición avanzada.
Este trabajo presenta un modelo de estimación de estado como parte integral del sistema SCADA. No obstante, el estimador de estado es no convexo. Por ende, se propone la aplicación de aproximaciones cónicas como Second order cone y Semidefinite programming para garantizar un óptimo global y unicidad de la solución. El modelo incluye medición directa del ángulo gracias al uso de medidores inteligentes
y micro unidades de medición fasorial micro-pmu. El modelo es evaluado en diferentes sistemas de prueba de la literatura científica internacional. Estos son cuantificados por métricas estocásticas que entregan la
diferencia entre el valor estimado y el real como root mean square error o el nivel de confianza empleado para verificar datos incorrectos y la confiabilidad del sistema. Además, el comportamiento de las micro-pmu se indaga con el total voltaje error. Estos resultados muestran una alta eficiencia garantizando un óptimo global y precisión al emplear cvxPy en Python.Contents
1 Introduction 10
1.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.2 Active distribution networks (ADNs) . . . . . . . . . . . . . . . . 12
1.3 The state estimation problem . . . . . . . . . . . . . . . . . . . . 14
1.4 Convex optimization-based Methods . . . . . . . . . . . . . . . . 15
1.5 Contribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.6 Outline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2 The state estimation problem in ADNs 19
2.1 Overview of the classic state estimation problem . . . . . . . . . 19
2.2 The state estimation as an optimization problem . . . . . . . . . 22
2.3 Available measurements in ADNs . . . . . . . . . . . . . . . . . . 24
2.4 SCADA systems . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.5 Phasor measurement units . . . . . . . . . . . . . . . . . . . . . . 27
2.6 Challenges in power distribution networks . . . . . . . . . . . . . 29
3 Convex model for the state estimation of ADNs 32
3.1 Convex optimization for state estimation . . . . . . . . . . . . . . 32
3.2 Convex cones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
3.3 Second-order cone programming . . . . . . . . . . . . . . . . . . 37
3.4 Application of SOC to the state estimation . . . . . . . . . . . . 38
3.5 Cone of Semidefinite matrices . . . . . . . . . . . . . . . . . . . . 40
6
Maria Valeria Fajardo Latorre Maria Valeria Fajardo Latorre
3.6 Application of SDP to the state estimation problem . . . . . . . 41
3.7 Stochastic metrics . . . . . . . . . . . . . . . . . . . . . . . . . . 42
3.7.1 Total vector error . . . . . . . . . . . . . . . . . . . . . . . 42
3.7.2 Root mean square error . . . . . . . . . . . . . . . . . . . 43
3.7.3 Confidence level criterion . . . . . . . . . . . . . . . . . . 43
4 Results 45
4.1 Test systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
4.2 Numerical results . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
4.3 Results for state estimation in different IEEE . . . . . . . . . . . 46
4.4 Confidence level criterion . . . . . . . . . . . . . . . . . . . . . . 54
4.5 Criterion of the voltage phasors . . . . . . . . . . . . . . . . . . . 55
4.6 Root-mean-square error . . . . . . . . . . . . . . . . . . . . . . . 56
4.7 Remarks in regard with the existing literature . . . . . . . . . . . 58
5 Conclusions 61MaestríaMagíster en Ingeniería Eléctric
How the latent geometry of a biological network provides information on its dynamics: the case of the gene network of chronic myeloid leukaemia
No full textBackground: The concept of the latent geometry of a network that can be represented as a graph has emerged from the classrooms of mathematicians and theoretical physicists to become an indispensable tool for determining the structural and dynamic properties of the network in many application areas, including contact networks, social networks, and especially biological networks. It is precisely latent geometry that we discuss in this article to show how the geometry of the metric space of the graph representing the network can influence its dynamics.Methods: We considered the transcriptome network of the Chronic Myeloid Laeukemia K562 cells. We modelled the gene network as a system of springs using a generalization of the Hooke’s law to n-dimension (n ≥ 1). We embedded the network, described by the matrix of spring’s stiffnesses, in Euclidean, hyperbolic, and spherical metric spaces to determine which one of these metric spaces best approximates the network’s latent geometry. We found that the gene network has hyperbolic latent geometry, and, based on this result, we proceeded to cluster the nodes according to their radial coordinate, that in this geometry represents the node popularity.Results: Clustering according to radial coordinate in a hyperbolic metric space when the input to network embedding procedure is the matrix of the stiffnesses of the spring representing the edges, allowed to identify the most popular genes that are also centres of effective spreading and passage of information through the entire network and can therefore be considered the drivers of its dynamics.Conclusion: The correct identification of the latent geometry of the network leads to experimentally confirmed clusters of genes drivers of the dynamics, and, because of this, it is a trustable mean to unveil important information on the dynamics of the network. Not considering the latent metric space of the network, or the assumption of a Euclidean space when this metric structure is not proven to be relevant to the network, especially for complex networks with hierarchical or modularised structure can lead to unreliable network analysis results
Formulation and evaluation of a project for the commercialization of an energizing chewing gum in the Bogotá city
No full textEste documento presenta el estudio de viabilidad para la comercialización de una goma de mascar energizante en la ciudad de Bogotá D.C Esta evaluación y formulación de proyecto tiene como objetivo presentarle al mercado una opción diferente, innovadora, práctica y eficaz de los energizantes sólidos ya existentes, pues en la actualidad las presentaciones más comunes de esos productos energizantes son las bebidas, geles y barras.Ingeniero industrialPregradoThis document presents the viability study for the commercialization of an energizing chewing gum in the Bogotá, D.C. The objective of this project evaluation and formulation is to present to the market a different, innovative, practical and effective option to the existing solid energizers, since currently the most common presentations of these energizing products are drinks, gels and bars
Mesa 5 Desafíos futuros
No full text30° Reunión anual Red PyMEs Mercosur. Evento académico de referencia en el estudio y desarrollo del sector de la pequeña y mediana empresa, cuyo propósito es promover el intercambio de conocimientos, generar propuestas de mejora para la gestión de las empresas y contribuir al crecimiento productivo de la región.
Contenido Mesa 5 Desafíos futuros:
-Factores críticos para el éxito de las mipymes argentinas. Lisana Martínez, Valeria Scherger, Hernán Vigier. Universidad Nacional del Sur, Universidad Provincial del Sudoeste, CONICET (0' 00")
-China y la industria automotriz sudamericana frente al nuevo paradigma de la movilidad eléctrica. Darío Vázquez, Micaela Carlini. Universidad Nacional del San Martín, Universidad Nacional de La Matanza, CONICET (31' 35")
-Análisis de la gestión del talento humano en las mipymes de Chaco y Corrientes. Caracterización considerando tamaño, sector, rendimiento, entorno competitivo e innovación. Silvina Blanque, Mariana Valdez, María Gabriela Latorre, Adriana Chávez. Universidad Nacional del Noreste (1 1' 25")Fil: Blanque, Silvina María. Universidad Nacional del Noreste; ArgentinaFil: Carlini Carranza, Micaela. Unversiad Nacional de La Matanza; ArgentinaFil: Chávez, Adriana Elizabeth. Universidad Nacional del Noreste; ArgentinaFil: Latorre, María Gabriela. Universidad Nacional del Noreste; ArgentinaFil: Martínez, Lisana B. Universidad Nacional del Sur. CONICET. Universidad Provincial del Sudoeste; ArgentinaFil: Scherger, Valeria. Universidad Nacional del Sur. CONICET. Universidad Provincial del Sudoeste; ArgentinaFil: Valdés, Mariana. Universidad Nacional del Noreste; ArgentinaFil: Vázquez, Darío. Universidad Nacional de San Martín. Universidad Nacional de La Matanza. CONICET; ArgentinaFil: Vigier, Hernán. Universidad Nacional del Sur. CONICET. Universidad Provincial del Sudoeste; Argentin
Mesa 5 Desafíos futuros
No full textEl objetivo de la Reunión Anual de la Red Pymes Mercosur es promover el intercambio de conocimientos, generar propuestas de mejora para la gestión de las empresas y contribuir al crecimiento productivo de la región. En esta ocasión (30ª) el lema es "Sustentabilidad e inteligencia artificial: nuevos ejes de la transformación productiva, territorial y sectorial de las Pymes".
Contenido Mesa 5 Desafío futuros:
-Factores críticos para el éxito de las mipymes argentinas. Lisana B. Martínez, Valeria Scherger, Hernán Vigier (inicio)
-China y la industria automotriz sudamericana frente al nuevo paradigma de la movilidad eléctrica. Darío Vázquez, Micaela Carlini Carranza (31' 31")
-Análisis de la gestión del talento humano en las mipymes de Chacho y Corrientes. Silvina María Blanque, Mariana Valdez, María Gabriela Latorre, Adriana Chávez (1 01' 24")Fil: Blanque, Silvina María. Universidad Nacional del Noreste; ArgentinaFil: Carlini Carranza, Micaela. Universidad Nacional de La Matanza; ArgentinaFil: Vázquez, Darío. Universidad Nacional de San Martín, CONICET, Universidad Nacional de La Matanza; ArgentinaFil: Martínez, Lisana B. Universidad Nacional de Sur, CONICET, Universidad Provincial del SudoesteFil: Scherger, Valeria. Universidad Nacional de Sur, CONICET, Universidad Provincial del SudoesteFil: Vigier, hernán. Universidad Nacional de Sur, CONICET, Universidad Provincial del SudoesteFil: Chávez, Adriana. Universidad Nacional del Noreste; ArgentinaFil: Latorre, María Gabriela. Universidad Nacional del Noreste; ArgentinaFil: Valdés, Mariana. Universidad Nacional del Noreste; Argentin
Il performance management nei Dipartimenti di salute mentale (DSM) : proposta di un cruscotto multidimensionale e prospettive di implementazione
No full textIl tema della misurazione e della valutazione delle performance delle attività sanitarie è oggi centrale non solo a livello aziendale ma anche a livello di singole partizioni organizzative. Dipartimenti, distretti, unità operative sono chiamate a sviluppare sistemi e strumenti di performance management basati sulle proprie esigenze informative, allo scopo di supportare il middle management a migliorarne la gestione e orientare i comportamenti dei clinici.
Questo lavoro di ricerca propone un cruscotto di valutazione delle performance costruito per i Dipartimenti di Salute Mentale, che mira a superare i gap riscontrati in letteratura e nell’applicazione pratica di sistemi di performance management destinati a tale tipologia di dipartimenti. La definizione e la validazione del cruscotto ha, inoltre, coinvolto esperti del settore tramite focus group. Nelle conclusioni sono discussi le prospettive e i limiti dell’applicazione del cruscotto multidimensionale.Performance management in Mental Health Departments: a proposal for a multidimensional dashboard and considerations for implementation. Performance management is a central topic for health care sector, not just at corporate level but also for each organizational unit. Clinical directorates, healthcare districts, and clinical units must develop performance management systems and tools based on their peculiar needs of data and information in order to support middle managers' decisions, and orient clinicians' behaviors. This research proposes a multidimensional dashboard for Mental Health Departments. The proposal aims to overcome literature gaps and failures in implementation of performance management tools in this sector. The definition and validation of the multidimensional dashboard have involved several experts through a series of focus group. In conclusion, the authors discuss prospects and limits for implementation of this multidimensional dashboard
LA LINGUA DI LUIGI EINAUDI FRA CLASSICISMO E PATHOS
No full textL’autrice fa una lettura linguistica dei testi di Luigi Einaudi, per individuare i caratteri lessicali, stilistici e retorici degli scritti dell’economista, del divulgatore, del giornalista, del presidente della Repubblica. Su di essi ha pesato a lungo l’etichetta di scrittore nitido, ordinato, algido. In realtà, sottoponendo la sua vastissima produzione scritta a un esame ravvicinato, emerge la straordinaria capacità nell’uso di modalità linguistiche varie: solennità sintattica e affabilità colloquiale, modi popolari e invenzioni lessicali, descrizioni a forti tinte e sobrietà estrema. Valeria Della Valle, The language of Luigi Einaudi between classicism and pathos, in Luigi Einaudi: economic freedom and social cohesion, by Alfredo Gigliobianco, Rome-Bari, 2010, p. 138-154. The author makes a linguistic reading of texts by Luigi Einaudi, to identify the lexical, stylistic and rhetorical characters of the writings of the economist, the popularizer, the journalist, the President of the Italian Republic. On them has long weighed the label of a crisp, neat, icy writer. In fact, subjecting its vast production on close examination, it reveals the extraordinary ability in the use of various language modes: solemnity, friendly conversational syntactic, lexical inventions and popular modes, descriptions with bright colors and extreme simplicity
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