Metabolic reaction network approach for CHO modelling culture

Projecte realitzat en col.laboració amb Kungliga Tekniska Högskolan. Bioprocess DepartmentAnimal cell culture has provided several beneficial improvements in the field of biotechnology. Nowadays, the engineers have focused their work in the optimization of cell cultures techniques. One important tool used is the simulation by computer since it is inexpensive, requires less time than other methods and it is a simple way of understanding the behaviour of the cells in a culture. This Thesis worked in the design of one simulator that describe the evolution over time of the extracellular metabolites and cell growth of CHO culture. A model that was designed using the concept of metabolic reaction network and the assumption of pseudo-steady state was checked and validated using diverse set of experimental data. In order to trigger different metabolic routes in the cells, these experiments were carried out varying amino acid composition in the medium. The metabolic reaction network was simplified and consisted in 38 reactions. The set of experimental data was simulated using a graphical interface design in the present Thesis. The model succeeded since the results were very satisfactory. The error was, in general, small and it was checked that the system could also detect the different metabolic pathways that the cells follow when the initial conditions are modified in many metabolites. The model can also be applied without the information of all the essential amino acids, obtaining highly satisfying results as well

Validation d'un modèle animal par imagerie TEP des récepteurs d'oestrogènes mammaires tumoraux

Le présent mémoire vise à apporter une contribution à la recherche dans la lutte contre le cancer du sein. Après un bref aperçu sur les causes et les facteurs de risque associés au cancer du sein, le mémoire s'attardera à étudier les outils de dépistage et de vérification de l'efficacité des traitements ayant cours. Parmi les outils existants, nous avons privilégié la modalité d'imagerie appelée tomographie d'émission par positrons (TEP). Il s'agit d'un procédé non envahissant et très prometteur qui permet de visualiser divers paramètres tumoraux au niveau moléculaire. Par exemple dans les cancers du sein nous pouvons, par TEP, détecter et quantifier les récepteurs d'estrogène (RE) en utilisant un marqueur comme le 16[alpha]-[[indice supérieur 18]F]fluoro-17[bêta]-estradiol (FES) qui se lie aux RE. De la même manière, le [indice supérieur 18] F-Fluorodéoxyglucose (FDG) nous permet de visualiser l'activité métabolique des tumeurs et de détecter la présence de nécroses. La TEP fournit donc des information importantes pour l'évaluation et le développement de nouvelles approches thérapeutiques."--Résumé abrégé pa UMI

On the preserved extremal structure of Lipschitz-free spaces

[EN] We characterize preserved extreme points of the unit ball of Lipschitz-free spaces F(X) in terms of simple geometric conditions on the underlying metric space (X,d). Namely, the preserved extreme points are the elementary molecules corresponding to pairs of points p,q in X such that the triangle inequality d(p,q)<=d(p,r)+d(q,r) is uniformly strict for r away from p,q. For compact X, this condition reduces to the triangle inequality being strict. As a consequence, we give an affirmative answer to a conjecture of N. Weaver that compact spaces are concave if and only if they have no triple of metrically aligned points, and we show that all extreme points are preserved for several classes of compact metric spaces X, including Hölder and countable compacta.The research of the second author was partially supported by MINECO grant MTM2014-57838-C2-1-P and Fundacion Seneca, Region de Murcia grant 19368/PI/14.Aliaga, RJ.; Guirao Sánchez, AJ. (2019). On the preserved extremal structure of Lipschitz-free spaces. Studia Mathematica. 245(1):1-14. https://doi.org/10.4064/sm170529-30-11S114245

Metabolic reaction network approach for CHO modelling culture

Projecte realitzat en col.laboració amb Kungliga Tekniska Högskolan. Bioprocess DepartmentAnimal cell culture has provided several beneficial improvements in the field of biotechnology. Nowadays, the engineers have focused their work in the optimization of cell cultures techniques. One important tool used is the simulation by computer since it is inexpensive, requires less time than other methods and it is a simple way of understanding the behaviour of the cells in a culture. This Thesis worked in the design of one simulator that describe the evolution over time of the extracellular metabolites and cell growth of CHO culture. A model that was designed using the concept of metabolic reaction network and the assumption of pseudo-steady state was checked and validated using diverse set of experimental data. In order to trigger different metabolic routes in the cells, these experiments were carried out varying amino acid composition in the medium. The metabolic reaction network was simplified and consisted in 38 reactions. The set of experimental data was simulated using a graphical interface design in the present Thesis. The model succeeded since the results were very satisfactory. The error was, in general, small and it was checked that the system could also detect the different metabolic pathways that the cells follow when the initial conditions are modified in many metabolites. The model can also be applied without the information of all the essential amino acids, obtaining highly satisfying results as well

Simplifying plant gene silencing and genome editing logistics by a one-Agrobacterium system for simultaneous delivery of multipartite virus vectors

Viral vectors provide a quick and effective way to express exogenous sequences in eukaryotic cells and to engineer eukaryotic genomes through the delivery of CRISPR/Cas components. Here, we present JoinTRV, an improved vector system based on tobacco rattle virus (TRV) that simplifies gene silencing and genome editing logistics. Our system consists of two mini T-DNA vectors from which TRV RNA1 (pLX-TRV1) and an engineered version of TRV RNA2 (pLX-TRV2) are expressed. The two vectors have compatible origins that allow their cotransformation and maintenance into a single Agrobacterium cell, as well as their simultaneous delivery to plants by a one-Agrobacterium/two-vector approach. The JoinTRV vectors are substantially smaller than those of any known TRV vector system, and pLX-TRV2 can be easily customized to express desired sequences by one-step digestion-ligation and homology-based cloning. The system was successfully used in Nicotiana benthamiana for launching TRV infection, for recombinant protein production, as well as for robust virus-induced gene silencing (VIGS) of endogenous transcripts using bacterial suspensions at low optical densities. JoinTRV-mediated delivery of single-guide RNAs in a Cas9 transgenic host allowed somatic cell editing efficiencies of ≈90%; editing events were heritable and >50% of the progeny seedlings showed mutations at the targeted loci

PANTOTHENIC ACID: AN OVERVIEW FOCUSED ON MEDICAL ASPECTS

Pantothenic acid (vitamin B5) is a water-soluble B-complex vitamin. It is of biologic importance because of its incorporation into coenzyme A and acyl carrier protein. Coenzyme A is an indispensable cofactor in all living organisms, where it functions in over 70 enzymatic pathways. Most bacteria, plants, and fungi synthesizes pantothenic acid; thus, the vitamin is found virtually everywhere in nature. Therefore, a naturally occurring vitamin deficiency in humans does not occur. Several clinical trials have been undertaken in humans using pantothenic acid supplementation in various medical fields. Unfortunately, firm conclusions regarding therapeutic effectiveness cannot be drawn from many of these studies. However, it has been suggested that there is a beneficial effect of pantethine on hyperlipidemia. Cysteamine treatment, a metabolite of the degradation of coenzyme A, has dramatically changed the course of the cystinosis; and clinical trials of this compound are underway in other medical fields. In the last few decades, several studies have pointed out the great interest of the inhibition of the coenzyme A metabolic pathway as an attractive target in developing new antimicrobial agents. Furthermore, recent research on coenzyme A metabolic enzymes has led to the discovery of uniquely nonmetabolic roles for both enzymes and their metabolites, thus opening an exciting field of investigation. In the present mini-review, we describe the current understanding of the pantothenic acid medical aspects and provide an overview on future potential therapeutic indications for this vitamin and its metabolic byproducts

The implant-supported milled bar overdenture : a literature review

Purpose: This bibliographical review aims to determine the present situation of the implant-supported milled bar overdenture as a therapeutic option in implantology, as well as to set and compare the techniques and materials currently used for making them. Materials and methods: By searching the main electronic bibliographical data in indexed Medline articles, we obtained a total number of 20 articles that fulfilled the requirements of this bibliographical review. Results: The implant-supported milled bar overdenture offers excellent long-term successful results, although complication rates are higher in emergency cases of patients initially planned for a fixed prosthesis. Krenmair and collaborators found cumulative survival rates of implants on milled bars after 5 years, of 99% in mandible cases, and of 97.8% in maxilla cases. No detailed protocols specifying the necessary number of implants or their characteristics have been found, though they are never made with less than 4 implants in mandible or 4-6 in the maxilla. Milled bars are screwed, generally cast in a precious metal alloy, with a metal or acrylic suprastructure and include attachments that regulate the tightness. The suprastructure adjusts precisely and rigidly to the milled bar, and presents similar biomechanical movements to those of fixed prostheses. The overdenture is removable and its prophylaxis is simple. Conclusions: The implant supported milled bar overdenture is a very interesting option in the treatment of patients with moderate to severe reabsorbed maxilla problems. It offers both the advantages of removable prostheses as well as the stability and retention of a fixed prosthesis

Características y pronóstico de los pacientes geriátricos en el Servicio de Cuidados Críticos del Hospital Nacional Guillermo Almenara Irigoyen - EsSalud en el año 2010

Introducción: Se realiza un trabajo descriptivo, retrospectivo, analítico y comparativo, para evaluar la morbimortalidad de los pacientes geriátricos, ingresados al Servicio de Cuidados Críticos del Hospital Guillermo Almenara Irigoyen durante el periodo 2010. Objetivo: Describir las características y los factores pronósticos de los pacientes Geriátricos ingresados al Servicio de Cuidados Críticos del Hospital Guillermo Almenara Irigoyen. Material y métodos: Se estudiaron un total de 213 pacientes mayores de 65 años, todos ellos ingresados a nuestro servicio por diferentes patologías clínicas y quirúrgicas. Se analizaron diferentes variables como son la edad, el sexo, la procedencia, las patologías previas, el motivo de ingreso, el estado funcional previo – Barthel, la mortalidad neta y el porcentaje de egresados vivos. Resultados: Como resultados del estudio, se observaron que el grupo etáreo más frecuente fue el mayor a 75 años, con predominio del sexo masculino, y las patologías más frecuentes encontradas fueron las enfermedades cardiovasculares seguidos de cerca de las enfermedades respiratorias. La mortalidad neta en el estudio fue similar a la mortalidad del grupo de individuos más jóvenes comparada con otras series y el índice de egresados vivos fue significativo. Los resultados fueron tabulados y procesados estadísticamente, creándose una base de datos computarizados. Conclusiones: Se puede notar que en los últimos años ha ocurrido un crecimiento relevante de la población geriátrica, y hay también un aumento en la incidencia de las enfermedades degenerativas, lo cual ha implicado un incremento de las necesidades de cuidados intensivos de estos pacientes. Al parecer la edad por sí sola no representa un criterio definitivo cuando se trata de seleccionar los potenciales beneficiarios del servicio y únicamente la severidad de la enfermedad, ha demostrado jugar un papel importante en la evolución del paciente crítico, por lo que se requieren de mayores estudios para definir la conducta del clínico cuando enfrenta a un paciente geriátrico critico que requiera manejo intensivo.Trabajo académic

Estrategia digital "Del casca a tu casa" como medio promocional del nuevo modelo de negocios de reparto a domicilio del restaurante El Cascajal

El siguiente trabajo profesional tuvo como finalidad desarrollar la estrategia digital "Del Casca a Tu Casa" como medio promocional del nuevo modelo de negocio de entrega a domicilio del restaurante El Cascajal, ofreciendo comida de calidad y entrega rápida, manteniendo protocolos de bioseguridad. Debido a la influencia de la pandemia en la ciudad de Lima, el sector empresarial tuvo que repensar sus modelos de negocio para no cerrar sus puertas. El Restaurante El Cascajal permitió aplicar diferentes enfoques estratégicos partiendo de un estudio basado en las preferencias de dos segmentos de clientes (corporativos y comensales). El análisis de las condiciones operativas del mercado y la competencia, aplicando elementos clave de la estrategia de comunicación digital. La definición de un plan estratégico, nueva identidad corporativa, imagen visual, canales de distribución, estrategias de medios y relación de los presupuestos proyectados versus los reales; a su vez, se realizó una evaluación para decidir la implementación de su propio servicio de entrega a domicilio en la ciudad de Lima. Fidelización, engagement, KPIs, fueron elementos clave en esta propuesta de comunicación digital, para tomar decisiones que se ajusten a la realidad y al posicionamiento del restaurante como referente en el sector gastronómico. La creación y los beneficios de estas estrategias les permitió seguir funcionando en tiempo de COVID-19.The following professional work had the purpose of developing the digital strategy "Del Casca a Tu Casa" as a promotional medium for the new business model of home delivery of the restaurant El Cascajal, offering quality food and fast delivery, while maintaining biosafety protocols. Because of the influence of the pandemic in the city of Lima, the business sector had to rethink its business models for not close its doors. El Cascajal Restaurant allowed applying different strategic approaches by starting with a study based on the preferences of two customer segments (corporate and diners). Conducting an analysis of the operating conditions of the market and competition, applying key elements of digital communication strategy. Ranging from the definition of a strategic plan, the new corporate identity, visual image, distribution channels, media strategies, and the relationship of projected versus actual budgets; in turn, an evaluation to decide the implementation of its own delivery service. Loyalty, engagement, KPIs, were key elements in this digital communication proposal, to make decisions that fit the reality and the positioning as a reference in the gastronomic sector. The creation and benefits of these strategies allowed the restaurant to continue working in time of COVID-19