Overcoming TGFβ-mediated immune evasion in cancer

This Review discusses the context-dependent functions of transforming growth factor-beta (TGF beta) with regard to the composition and behaviour of different cell populations in the tumour immune microenvironment, as well as emerging data that demonstrate that TGF beta inhibition can restore cancer immunity. Transforming growth factor-beta (TGF beta) signalling controls multiple cell fate decisions during development and tissue homeostasis; hence, dysregulation of this pathway can drive several diseases, including cancer. Here we discuss the influence that TGF beta exerts on the composition and behaviour of different cell populations present in the tumour immune microenvironment, and the context-dependent functions of this cytokine in suppressing or promoting cancer. During homeostasis, TGF beta controls inflammatory responses triggered by exposure to the outside milieu in barrier tissues. Lack of TGF beta exacerbates inflammation, leading to tissue damage and cellular transformation. In contrast, as tumours progress, they leverage TGF beta to drive an unrestrained wound-healing programme in cancer-associated fibroblasts, as well as to suppress the adaptive immune system and the innate immune system. In consonance with this key role in reprogramming the tumour microenvironment, emerging data demonstrate that TGF beta-inhibitory therapies can restore cancer immunity. Indeed, this approach can synergize with other immunotherapies - including immune checkpoint blockade - to unleash robust antitumour immune responses in preclinical cancer models. Despite initial challenges in clinical translation, these findings have sparked the development of multiple therapeutic strategies that inhibit the TGF beta pathway, many of which are currently in clinical evaluation

Estudio de Mercado para explorar el potencial de la apertura de una oferta académica en el área de Tecnologías de Información y Comunicación en la SedeRegional San Carlos del Instituto Tecnológico de Costa Rica, a agosto del 2008

Proyecto de Graduación (Bachillerato en Administración de Empresas) Instituto Tecnológico de Costa Rica, Escuela Administración de Empresas, 2008El presente estudio pretende explorar el potencial de mercado para la apertura de una oferta académica en el área de Tecnologías de Información y Comunicación en la Sede Regional San Carlos del Instituto Tecnológico de Costa Rica, a agosto del 2008. El estudio está basado en tres fuerzas competitivas que son: Proveedores de la Industria, Rivalidad de la Industria y Compradores de la Industria. Las cuales se estudiaron por separado. En el estudio de los Proveedores de la Industria se analizó el comportamiento del proceso de admisión del ITCR en general y específicamente de la Escuela de Computación y Computación San Carlos. De esta manera se pudo identificar aspectos como el flujo de estudiantes en el proceso de admisión, la condición de género, la posición geográfica, la nota de admisión, y los colegios que aportaron más estudiantes potenciales al proceso de admisión en el periodo 2003-2008. Para el análisis de la Rivalidad de la Industria se consideraron todas las ofertas académicas en el áreas de TICs que ofrecen actualmente las universidades públicas y privadas del país, lo que se pretendía era caracterizar las ofertas de TICs que existen en el mercado. Por último se estudiaron a los Compradores de la Industria, que en este caso está formado por las empresas que podrían ser los empleadores de los profesionales en TICs. Para los cual se tomó en cuenta a empresas de diversos sectores económicos a las cuales se les hizo una entrevista personal con el fin de conocer que pensaban sobre el perfil de los profesionales en Tecnologías de Información y Comunicación que se necesita en sus empresas y en el país en general

Una aproximación funcional al estudio de la interacción verbal en terapia

Tesis doctoral inédita leida en la Universidad Autónoma de Madrid, Facultad de Psicología. Departamento de Psicología Biológica y de la Salud. Fecha de lectura: 6 de mayo de 2011

Control architecture of the ATLAS 2020 lower-limb active orthosis

This paper outlines the control details implemented in the wearable gait exoskeleton ATLAS 2020 for improving the therapy of SMA children. This paper discusses the control challenges of a gait-training wearable exoskeleton for SMA children. Such device would also increase these children's quality of life, achieving a reduction of disability and increased functional independence.Peer reviewe

Patrones de interacción verbal en el contexto clínico: un modelo de cómo la gente cambia en terapia

Antecedentes: el artículo publicado en esta revista “¿Por qué la gente cambia en terapia? Un estudio preliminar” (2006) supuso el inicio de una línea de investigación basada en metodología observacional, dirigida a clarifi car el proceso terapéutico. A lo largo de estos años han sido grandes los avances en la explicación del cambio clínico. En este artículo se presenta una síntesis de esta línea de investigación, aportando una serie de conclusiones que, en cierta medida, dan respuesta a muchos de los interrogantes que presentábamos en ese primer trabajo al que hacíamos referencia. Método: se registró la conducta verbal de terapeutas y clientes en 92 sesiones clínicas, mediante el sistema de categorización de la interacción de la conducta verbal en terapia (SISC- INTER- CVT). A continuación, se realizó un análisis descriptivo y secuencial de las observaciones. Resultados: los datos mostraron la existencia de ciertos patrones de interacción verbal, relacionados con las actividades clínicamente relevantes desempeñadas por el terapeuta, a partir de los cuales se desarrolló un modelo de interacción verbal en el contexto clínico. Conclusiones: el análisis funcional de la interacción verbal terapeuta-cliente resulta imprescindible para comprender los procesos que explican el cambio clínico y aumentar la calidad de la terapia psicológicaBackground: The paper “Why do people change in therapy? A preliminary study” (2006), published in this journal, led to the beginning of a line of research based on observational methodology and aimed at the clarifi cation of the therapeutic process. Throughout these years, signifi cant progress has been made towards an explanation of clinical change. In this paper, a synthesis of this line of research is presented, along with a series of conclusions that can, to some extent, provide an answer to the questions we posed in the aforementioned fi rst paper. Method: Verbal behavior both of therapist and client was coded for 92 clinical sessions using the Verbal Behavior Interaction Category System (SISC-INTER-CVT). Descriptive and sequential analyses of the observations were then performed. Results: The data show the existence of certain patterns of verbal interaction that are related to the clinically relevant activities undertaken by the therapist, from which a model for verbal interaction in the clinical context was developed. Conclusions: The functional analysis of the therapist-client verbal interaction is essential for the comprehension of the processes that explain clinical change as well as for the improvement of the quality of psychological therapyFinancial support was received from the Spanish Government (Science and Innovation Ministry, I +D+ I Research Grant, SEJ2007-66537-PSIC, PSI2010-15908

Functional analysis of the verbal interaction between psychologist and client during the therapeutic process

The goal of this study is to analyze the verbal interaction that takes place between client and therapist over the course of a clinical intervention so as to analyze the potential learning processes that may be responsible for changes in the client's behavior. A total of 92 sessions were analyzed, corresponding to 19 clinical cases treated by 9 therapists specializing in behavioral therapy. The variables considered were therapist and client verbal behaviors, and these were categorized according to their possible functions and/or morphologies. The Observer XT software was used as a tool for the observational analysis. The results led to the conclusion that the therapist responds differentially to client verbalizations, modifying the verbal contingencies as his or her client content approaches or becomes more distant from therapeutic objectives. These results suggest the possible existence of verbal "shaping" processes through which the therapist guides the client's verbal behavior toward more adaptive forms. In addition, this study proposes an alternative to the traditional controversy regarding the relevance of the therapeutic relationship versus the treatment techniques used to explain clinical change. This article suggests that such differentiation is unnecessary because the therapeutic relationship and the treatment techniques should act in the same manner, this is, in providing the context for the occurrence of what is truly therapeutic, namely, the learning processe

Comparison of Retinal Nerve Fiber Layer Thickness Measurements in Healthy Subjects Using Fourier and Time Domain Optical Coherence Tomography

Purpose. To compare the retinal nerve fiber layer (RNFL) measurements using two different ocular coherence tomography (OCT) devices: Cirrus Fourier domain OCT and Stratus time domain OCT. To analyze reproducibility of Fourier domain measurements in healthy subjects. Methods. One hundred and thirty-two eyes of 132 healthy subjects were scaned on the same day with both instruments, separated by 10 minutes from each other. Thickness of quadrant, average and the 12 different areas around the optic nerve were compared between Cirrus and Stratus. Repeatability, intraclass correlation coefficients (ICCs), and coefficients of variation (COVs) were calculated in RNFL measurements provided by Fourier domain device. Results. The average thickness in the optic cube was 95.50 μm using Cirrus and 97.85 μm using Stratus. Average thickness and temporal quadrant showed significant differences using Cirrus and Stratus methods. Reproducibility was better with Fourier domain OCT (mean COV of 4.54%) than with Stratus time-domain OCT (mean COV of 5.57%). Conclusions. Both scan options give reproducible RNFL thickness measurement, but there are differences between them. Measurements obtained using Fourier domain device show better reproducibility

Characterisation of Grasp Quality Metrics

Robot grasp quality metrics are used to evaluate, compare and select robotic grasp configurations. Many of them have been proposed based on a diversity of underlying principles and to assess different aspects of the grasp configurations. As a consequence, some of them provide similar information but other can provide completely different assessments. Combinations of metrics have been proposed in order to provide global indexes, but these attempts have shown the difficulties of merging metrics with different numerical ranges and even physical units. All these studies have raised the need of a deeper knowledge in order to determine independent grasp quality metrics which enable a global assessment of a grasp, and a way to combine them. This paper presents an exhaustive study in order to provide numerical evidence for these issues. Ten quality metrics are used to evaluate a set of grasps planned by a simulator for 7 different robot hands over a set of 126 object models. Three statistical analysis, namely, variability, correlation and sensitivity, are performed over this extensive database. Results and graphs presented allow to set practical thresholds for each quality metric, select independent metrics, and determine the robustness of each metric,providing a reliability indicator under pose uncertainty. The results from this paper are intended to serve as guidance for practical use of quality metrics by researchers on grasp planning algorithms

El marketing en las organizaciones no lucrativas: el caso de Haritzalde

El propósito de este trabajo es buscar, analizar y entender, con la ayuda del caso Haritzalde, el uso de marketing en el ámbito no lucrativo. Al entender las diferencias que se pueden encontrar, comprender el punto de vista por el cuál enfocar la organización, e identificar sus puntos fuertes y débiles, de esta manera los gestores de las organizaciones podrán trabajar de una manera más efectiva. Este trabajo está enfocado a un cierto tipo de organizaciones no lucrativas (ONL) con el fin de estudiar a fondo el caso, pero muchas de las ideas se pueden aplicar a un ámbito más amplio

Role of UEV-1A, a homologue of the tumor suppressor protein TSG101, in protection from DNA damage

AbstractThe open reading frame YGL087c in the budding yeast Saccharomyces cerevisiae genome encodes a polypeptide highly similar to the human UEV (ubiquitin-conjugating E2 enzyme variant) proteins, which have been proposed to belong to a family of putative dominant negative ubiquitin regulators. Deletion of the YGL087c open reading frame yields viable cells which are sensitive to UV irradiation or methyl methanesulfonate, but not to hydroxyurea. This phenotype is reminiscent of that of rad mutants and suggests that the YGL087c-encoded protein functions in a process related to tolerance to DNA damage. We also show that the mutant phenotype is fully complemented by expression of the human UEV-1A cDNA and we propose that UEV-1 proteins could also have a role in protecting higher eukaryotic cells from DNA damaging agents