Coevolution of RAC Small GTPases and their Regulators GEF Proteins.

RAC proteins are small GTPases involved in important cellular processes in eukaryotes, and their deregulation may contribute to cancer. Activation of RAC proteins is regulated by DOCK and DBL protein families of guanine nucleotide exchange factors (GEFs). Although DOCK and DBL proteins act as GEFs on RAC proteins, DOCK and DBL family members are evolutionarily unrelated. To understand how DBL and DOCK families perform the same function on RAC proteins despite their unrelated primary structure, phylogenetic analyses of the RAC, DBL, and DOCK families were implemented, and interaction patterns that may suggest a coevolutionary process were searched. Interestingly, while RAC and DOCK proteins are very well conserved in humans and among eukaryotes, DBL proteins are highly divergent. Moreover, correlation analyses of the phylogenetic distances of RAC and GEF proteins and covariation analyses between residues in the interacting domains showed significant coevolution rates for both RAC-DOCK and RAC-DBL interactions.A.J.S. was supported by the Mexican National Council of Science and Technology (CONACyT), the Mexican Secretariat of Public Education (SEP), and the Cancer Research UK.This is the final version of the article. It first appeared from Libertas Academica via http://dx.doi.org/10.4137/EBO.S3803

Automated Home Oxygen Delivery for Patients with COPD and Respiratory Failure: A New Approach

Long-term oxygen therapy (LTOT) has become standard care for the treatment of patients with chronic obstructive pulmonary disease (COPD) and other severe hypoxemic lung diseases. The use of new portable O-2 concentrators (POC) in LTOT is being expanded. However, the issue of oxygen titration is not always properly addressed, since POCs rely on proper use by patients. The robustness of algorithms and the limited reliability of current oximetry sensors are hindering the effectiveness of new approaches to closed-loop POCs based on the feedback of blood oxygen saturation. In this study, a novel intelligent portable oxygen concentrator (iPOC) is described. The presented iPOC is capable of adjusting the O-2 flow automatically by real-time classifying the intensity of a patient's physical activity (PA). It was designed with a group of patients with COPD and stable chronic respiratory failure. The technical pilot test showed a weighted accuracy of 91.1% in updating the O-2 flow automatically according to medical prescriptions, and a general improvement in oxygenation compared to conventional POCs. In addition, the usability achieved was high, which indicated a significant degree of user satisfaction. This iPOC may have important benefits, including improved oxygenation, increased compliance with therapy recommendations, and the promotion of PA

FACTORES DE EFICIENCIA DEL PERSONAL PARA EL DESARROLLO: ALCANCES Y LIMITACIONES

En el contexto de la reestructuración económica orientada por el neoliberalismo económico mundial, la creciente masa de desocupados y una sobreoferta de mano de obra, la eficiencia económica se ha tornado en una necesaria obsesión permanente y sistemática, —cuyo determinante central deviene del papel y uso que, específicamente, la fuerza laboral o “capital humano” desempeña— lo cual origina, entre otros elementos, una demanda de fuerza humana de trabajo, cuyos segmentos requieren de un mayor o menor grado de calificación para el desempeño laboral. En dicho contexto, se elevan los requisitos de calificación, por encima de los realmente requeridos por los puestos de trabajo, con la intención de obtener efectos específicos de eficacia y eficiencia en relación con la misma fuerza laboral, las empresas y el conjunto social, lo cual no sólo implica costos para esos tres órdenes (la fuerza laboral, las empresas y el conjunto social) sino que, a su vez, inciden en su propia competitividad y en resultados favorables o no, para el desarrollo regional y local. La reflexión crítica en torno a las nociones de productividad social y la precisión de los factores determinantes de eficacia y eficiencia de la fuerza de trabajo calificada, como el capital social más importante del desarrollo, permite no sólo construir o reconstruir el corpus teórico metodológico sino la praxis misma, de lo cual penden, no sólo los resultados prácticos de las empresas en particular, sino además, la restructuración económica, el desarrollo local y el regional

LAS POLÍTICAS PÚBLICAS PARA MITIGAR LA POBREZA EN LA ZONA METROPOLITANA PUEBLA-TLAXCALA

En los últimos cincuenta años en México se han aplicado políticas de Gobierno que, se podrían resumir en lo siguiente: Un primer periodo, de 1940-1955, considerado como desarrollo con inflación; segundo, 1955-1970, considerado como desarrollo sin inflación y1970-1982, este último como parte de reorganización del capitalismo mexicano. Posterior a ello, se consideran 37 años de políticas neoliberales estas, comparadas con el periodo 1940-1980, donde se aprecia un cambio en política pública de Gobierno, al pasar del Estado benefactor al Estado Neoliberal. Por su parte el Gobierno neoliberal, no ha mostrado sensibilidad ante los retos de la pobreza en el país. Así, solo instrumenta y legaliza la brecha entre ricos y pobres en el país. Tales políticas muestran la incapacidad del modelo económico, el cual no garantiza el desarrollo económico y social pretendido; más bien muestran un patrón de acumulación de capital agotado. En México, durante los últimos cinco sexenios, no se logró rebasar en promedio el 1.5% del PIB, ha sido incapaz de crear empleos suficientes y bien remunerados; por el contrario, ha generado tasas de desempleo en promedio 5.6% de la tasa de desempleo abierto (TDA) y 56 millones de mexicanos viviendo en la pobreza. El objetivo del trabajo se centra en el contexto de las políticas públicas que se proponen comprimir la pobreza en territorio mexicano. Así, como de los problemas más imperiosos en el desarrollo económico de Puebla y su Zona Metropolitana. Si el Gobierno cambia la orientación de las políticas neoliberales, puede mejorar los niveles de pobreza en la ZMCP.T

Characterisation of the Tumour Microenvironment in Ovarian Cancer

The tumour microenvironment comprises the non-cancerous cells present in the tumour mass (fibroblasts, endothelial, and immune cells), as well as signalling molecules and extracellular matrix. Tumour growth, invasion, metastasis, and response to therapy are influenced by the tumour microenvironment. Therefore, characterising the cellular and molecular components of the tumour microenvironment, and understanding how they influence tumour progression, represent a crucial aim for the success of cancer therapies. High-grade serous ovarian cancer provides an excellent opportunity to systematically study the tumour microenvironment due to its clinical presentation of advanced disseminated disease and debulking surgery being standard of care. This thesis first presents a case report of a long-term survivor (>10 years) of metastatic high-grade serous ovarian cancer who exhibited concomitant regression/progression of the metastatic lesions (5 samples). We found that progressing metastases were characterized by immune cell exclusion, whereas regressing metastases were infiltrated by CD8+ and CD4+ T cells. Through a T cell - neoepitope challenge assay we demonstrated that pre- dicted neoepitopes were recognised by the CD8+ T cells obtained from blood drawn from the patient, suggesting that regressing tumours were subjected to immune attack. Immune excluded tumours presented a higher expression of immunosuppressive Wnt signalling, while infiltrated tumours showed a higher expression of the T cell chemoattractant CXCL9 and evidence of immunoediting. These findings suggest that multiple distinct tumour immune microenvironments can co-exist within a single individual and may explain in part the hetero- geneous fates of metastatic lesions often observed in the clinic post-therapy. Second, this thesis explores the prevalence of intra-patient tumour microenvironment het- erogeneity in high-grade serous ovarian cancer at diagnosis (38 samples from 8 patients), as well as the effect of chemotherapy on the tumour microenvironment (80 paired samples from 40 patients). Whole transcriptome analysis and image-based quantification of T cells from treatment-naive tumours revealed highly prevalent variability in immune signalling and distinct immune microenvironments co-existing within the same individuals at diagnosis. ConsensusTME, a method that generates consensus immune and stromal cell gene signatures by intersecting state-of-the-art deconvolution methods that predict immune cell populations using bulk RNA data was developed. ConsensusTME improved accuracy and sensitivity of T cell and leukocyte deconvolutions in ovarian cancer samples. As previously observed in the case report, Wnt signalling expression positively correlated with immune cell exclusion. To evaluate the effect of chemotherapy on the tumour microenvironment, we compared site-matched and site-unmatched tumours before and after neoadjuvant chemotherapy. Site- matched samples showed increased cytotoxic immune activation and oligoclonal expansion of T cells after chemotherapy, unlike site-unmatched samples where heterogeneity could not be accounted for. In addition, low levels of immune activation pre-chemotherapy were found to be correlated with immune activation upon chemotherapy treatment. These results cor- roborate that the tumour-immune interface in advanced high-grade serous ovarian cancer is intrinsically heterogeneous, and that chemotherapy induces an immunogenic effect mediated by cytotoxic cells. Finally, the different deconvolution methods were benchmarked along with ConsensusTME in a pan-cancer setting by comparing deconvolution scores to DNA-based purity scores, leukocyte methylation data, and tumour infiltrating lymphocyte counts from image analysis. In so far as it has been benchmarked, unlike the other methods, ConsensusTME performs consistently among the top three methods across cancer-related benchmarks. Additionally, ConsensusTME provides a dynamic and evolvable framework that can integrate newer de- convolution tools and benchmark their performance against itself, thus generating an ever updated version. Overall, this thesis presents a systematic characterisation of the tumour microenvironment of high grade serous ovarian cancer in treatment-naive and chemotherapy treated samples, and puts forward the development of an integrative computational method for the systematic analysis of the tumour microenvironment of different tumour types using bulk RNA data.Cancer Research UK Cambridge Institute provided funding for my studentship. The Mexican National Council of Science and Technology provided funding for my studentship

Game for learning data structures and algorithms

Trabajo de Fin de Grado en Doble Grado en Ingeniería Informática y Matemáticas, Facultad de Informática UCM, Departamento de Ingeniería del Software e Inteligencia Artificial, Curso 2020/2021Las asignaturas de algoritmos y estructuras de datos son una parte fundamental en los estudios de informática. En una primera aproximación a ellas, el alumno puede tener dificultades en su comprensión. Es por ello que puede ser buena idea disminuir el nivel de abstracción, elegir un caso concreto y mostrar la aplicación del algoritmo a dicho ejemplo. Además, numerosos estudios están a favor de que sea también el estudiante el que aprende por sí mismo mediante la interacción con un juego relacionado con el concepto a estudiar. Es por ello que se implementa una aplicación en Unity que muestra las ideas principales de algunos de los algoritmos básicos y estructuras de datos típicas, y que no se limita a mostrar su funcionamiento, sino que permite la interacción del usuario, guardando también estadísticas sobre su rendimiento. En esta memoria se explican inicialmente los objetivos y las aplicaciones similares existentes. En los capítulos siguientes, se describe el desarrollo de la aplicación. Primero, se centra en cada juego implementado y la interacción pedida al usuario en cada caso; después, en los aspectos del diseño y desarrollo de la aplicación. La memoria finaliza con los resultados de las pruebas con usuarios.Algorithms and data structures are core subjects in computer science courses. In a first approach, the student may find them difficult. In consequence, it could be a good idea to use a lower level of abstraction, choose a concrete example and show the flow of the algorithm applied to that case. In addition, there are a lot of articles that uphold the benefits for the students if they interact with a game about these concepts. Therefore, a Unity game has been developed in order to show the main concepts of these most common algorithms and data structures. It allows users to interact with it to make learning more attractive, and saves data about their performance. In this work, initially, the aims of the application are explained, and similar games are analyzed. Then, there are two chapters about the development of the application. The first one is focused on the games that are implemented and the user interaction. The second one explains the design and the development of the game. Finally, the outcomes of the usability tests are shown.Depto. de Ingeniería de Software e Inteligencia Artificial (ISIA)Fac. de InformáticaTRUEunpu

Hardware/software codesign methodology for fuzzy controller implementation

This paper describes a HW/SW codesign methodology for the implementation of fuzzy controllers on a platform composed by a general-purpose microcontroller and specific processing elements implemented on FPGAs or ASICs. The different phases of the methodology, as well as the CAD tools used in each design stage, are presented, with emphasis on the fuzzy system development environment Xfuzzy. Also included is a practical application of the described methodology for the development of a fuzzy controller for a dosage system

Evaluación del desajuste educativo en la industria hostelera española

For decades, academics have studied the human resources of many different sectors with a wide range of approaches and methodologies. However, there is still room for analysis on educational mismatch, even more so in the hospitality industry after the COVID-19 pandemic standstill as it is a topic that has been somewhat relegated in recent times. Thus, this study seeks to analyze this phenomenon based on a multinomial logistic regression, which is underused in the human capital-related literature, especially on educational mismatch. The results confirm the influence of several factors such as tenure, experience or skills and quantify their effects on the chances of being educationally mismatched. Moreover, special attention is given to the remarkable influence of the required skills for a specific job position on vertical mismatch. Therefore, this paper updates previous research on the issue but also sheds new light on identifying the main aspects in which employees may focus in order to have better career prospects. The main limitation of this study is the availability of the data, which corresponds to 2018.Durante décadas, los académicos han estudiado los recursos humanos de muchos sectores diferentes con una amplia gama de enfoques y metodologías. Sin embargo, todavía hay espacio para el análisis del desajuste educativo, más aún en la industria de la hostelería tras el parón de la pandemia COVID-19, ya que es un tema que ha quedado ligeramente relegado en los últimos tiempos. Así pues, este estudio pretende analizar este fenómeno a través de una regresión logística multinomial, una metodología que se encuentra infrautilizada en la literatura relacionada con el capital humano, especialmente en el desajuste educativo. Los resultados confirman la influencia de varios factores, como la antigüedad en el puesto, la experiencia o las competencias, y cuantifican sus efectos sobre las posibilidades de sufrir desajuste educativo. Además, se presta especial atención a la gran influencia de las competencias requeridas para un puesto de trabajo específico sobre el desajuste vertical. Así pues, este trabajo actualiza las investigaciones anteriores sobre la cuestión, pero también arroja nueva luz sobre la identificación de los principales aspectos en los que los empleados podrían prestar atención para tener mejores perspectivas de carrera. La principal limitación de este trabajo es la disponibilidad de los datos, que corresponden a 2018.Sánchez-Cubo, F. benefits from a predoctoral contract for training researcher staff within the frame of the Formación de Profesorado Universitario (FPU) Fellowship Programme of the Ministry of Universities of Spain

Controladores difusos adaptativos como módulos de propiedad intelectual para FPGAs

La continua demanda por parte del mercado microelectrónico de aplicaciones novedosas, con elevados niveles de complejidad y tiempos de desarrollo cortos ha motivado el impulso de las técnicas de diseño basadas en el concepto de “reusabilidad” y el desarrollo de elementos de sistemas como módulos de propiedad intelectual o módulos IP. En esta comunicación se describe la implementación de controladores difusos como módulos IP para FPGAs. Los controladores operan como periféricos conectables al bus OPB para los procesadores disponibles en las FPGAs de Xilinx. El empleo de las memorias internas de las FPGAs para almacenar las bases de conocimiento permite definir o ajustar la funcionalidad en tiempo de operación.Ministerio de Educaión y Ciencia TEC2005-04359/MI