297 research outputs found

    From Individual to Organizational Resilience, A Case Study Review

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    Major disasters, both natural and human-made, pose sometimes insurmountable problems for unprepared or under-prepared organizations. In this capstone I explore and develop ideas about how individuals are able to affect organizational dynamics, within a complex context of change, in order to facilitate the mechanism of resilience. I employ the enriching information from a review of literature and my Organizational Dynamics classes. I use case studies of Sandler O’Neill’s response to the World Trade Center tragedy and the development of the Oregon Resilience Plan to identify a systemic approach to understanding the complexity of current organizational environments and the power of organizations’ dexterities. Further studies are needed to transfer theoretical resilience into practice, thereby developing organizations’ ability to change in such a way that becoming a new entity may be not only valuable but also affordable

    Introduction

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    The fate of murine double minute X (MdmX) is dictated by distinct signaling pathways through murine double minute 2 (Mdm2)

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    Mouse double minute 2 (Mdm2) and MdmX dimerize in response to low levels of genotoxic stress to function in a ubiquitinating complex, which signals for destabilization of p53. Under growth conditions, Mdm2 functions as a neddylating ligase, but the importance and extent of MdmX involvement in this process are largely unknown. Here we show that when Mdm2 functions as a neddylating enzyme, MdmX is stabilized. Furthermore, we demonstrate that under growth conditions, MdmX enhances the neddylation activity of Mdm2 on p53 and is a substrate for neddylation itself. Importantly, MdmX knockdown in MCF-7 breast cancer cells resulted in diminished neddylated p53, suggesting that MdmX is important for Mdm2-mediated neddylation. Supporting this finding, the lack of MdmX in transient assays or in p53/MdmX-/- MEFs results in decreased or altered neddylation of p53 respectively; therefore, MdmX is a critical component of the Mdm2-mediated neddylating complex. c-Src is the upstream activator of this Mdm2-MdmX neddylating pathway and loss of Src signaling leads to the destabilization of MdmX that is dependent on the RING (Really Interesting New Gene) domain of MdmX. Treatment with a small molecule inhibitor of neddylation, MLN4924, results in the activation of Ataxia Telangiectasia Mutated (ATM). ATM phosphorylates Mdm2, converting Mdm2 to a ubiquitinating enzyme which leads to the destabilization of MdmX. These data show how distinct signaling pathways engage neddylating or ubiquitinating activities and impact the Mdm2-MdmX axis

    Automated low-cost device to produce sub-micrometric polymer fibers based on blow spun method

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    Attending the latest advances in polymeric fibers, the design of low-cost, and high-quality scientific equipment for obtaining fibers seemed essential. To overcome this challenge, a 3D printable prototype was designed, assembled, and validated to obtain fibers using the SBS method. The particular configuration of the prototype consisted of controlling the process conditions such as working distance and injection flow, as well as other parameters such as RPM and the axial movement of the cylindrical collector. Thus, these parameters were automated using a microcontroller (Arduino) that receives information from an Android device with bluetooth connectivity to control each of the elements of the equipment. Subsequently, the repeatability and reproducibility of the fibers was verified using polymers such as polystyrene (PS), polysulfone (PSF) and polyethylene oxide (PEO); furthermore, PSF fibers were manufactured to analyze the influence of working distance and the axial movement of the collector on their production.Fondos de Investigación de Fco. Javier González Benito, política de reinversión de costes generales, Universidad Carlos III de Madrid [2012/00130/004] and Acción Estratégica en Materiales Compuestos Poliméricos e Interfases, Universidad Carlos III de Madrid [2011/00287/002]. Besides, authors greatly appreciate the Consejo Nacional de Ciencia y Tecnología (CONACyT- México) for financial support associated to the scholarship number 625396

    Early-Stage Metastasis Requires Mdm2 and Not p53 Gain of Function

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    Metastasis of cancer cells to distant organ systems is a complex process that is initiated with the programming of cells in the primary tumor. The formation of distant metastatic foci is correlated with poor prognosis and limited effective treatment options. We and others have correlated Mouse double minute 2 (Mdm2) with metastasis; however, the mechanisms involved have not been elucidated. Here, it is reported that shRNA-mediated silencing of Mdm2 inhibits epithelial–mesenchymal transition (EMT) and cell migration. In vivo analysis demonstrates that silencing Mdm2 in both post-EMT and basal/triple-negative breast cancers resulted in decreased primary tumor vasculature, circulating tumor cells, and metastatic lung foci. Combined, these results demonstrate the importance of Mdm2 in orchestrating the initial stages of migration and metastasis

    Microwave Assisted Synthesis of Py-Im Polyamides

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    Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chemistry on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification. It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several additional coupling steps

    Distribución espacial y temporal de tortugas marinas asociada a la temperatura superficial del mar y clorofila-a en aguas del Pacífico Central Mexicano

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    In this study we describe the spatial and temporal distribution of sea turtles and their association with oceanographic parameters in waters of the Mexican Central Pacific (MCP) during 2010 (winter, spring and autumn). Our results showed variations in sea turtle distribution through the sampling year. Sea turtle distribution was homogeneous in coastal and oceanic areas during winter; there was an association with thermal fronts generated by a current of cold water flowing from the northwest and a warm current coming from the south, as well as with the boundaries of a cyclonic gyre. Sea turtles were distributed in the coastal zone and the central part of the oceanic zone in spring, where the effects of a cyclonic gyre and coastal upwelling prevailed. The same distribution trend was recorded at the beginning of autumn, whereas oceanographic characteristics changed during the second sampling week, when upwelling occurred. Mating events were only recorded in autumn for olive ridley sea turtles (Lepidochelys olivacea), the dominant species in the region. It was concluded that sea turtles were distributed in the coastal zone of MCP waters in autumn due to reproductive activities, whereas in winter and spring sea turtles were distributed towards the central/oceanic region, potentially related to foraging activities.En este estudio se describe la distribución espacio-temporal de tortugas marinas y su relación con parámetros oceanográficos en el Pacífico Central Mexicano (PCM) durante el 2010 (invierno, primavera y otoño). Los resultados muestran variaciones en la distribución de tortugas marinas. En invierno, la distribución de tortugas fue homogénea en áreas costeras y oceánicas; asociadas a la presencia de frentes térmicos debido a la interacción de una corriente de agua cálida del sur y la intrusión de agua fría proveniente del noroeste, así como con los límites de un giro ciclónico. En primavera, la distribución de tortugas se concentró hacia la zona costera y parte central de la zona oceánica, donde prevalecieron los efectos de una surgencia y los límites de un giro ciclónico. El mismo patrón de distribución ocurrió al inicio de otoño, mientras que las condiciones oceanográficas cambiaron para la segunda semana de muestreo, cuando ocurrió la formación de una surgencia costera. Los eventos de apareamiento solo se registraron durante otoño para la tortuga golfina (Lepidochelys olivacea), la especie dominante de la región. Se concluye que en otoño el patrón de distribución de tortugas marinas fue hacia la zona costera del PCM, y se relacionó con actividades de reproducción; mientras que en invierno y primavera este patrón tendió a la región central/oceánica vinculado potencialmente con actividades de forrajeo

    The proto‐oncogene function of Mdm2 in bone

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    Mouse double minute 2 (Mdm2) is a multifaceted oncoprotein that is highly regulated with distinct domains capable of cellular transformation. Loss of Mdm2 is embryonically lethal, making it difficult to study in a mouse model without additional genetic alterations. Global overexpression through increased Mdm2 gene copy number (Mdm2Tg) results in the development of hematopoietic neoplasms and sarcomas in adult animals. In these mice, we found an increase in osteoblastogenesis, differentiation, and a high bone mass phenotype. Since it was difficult to discern the cell lineage that generated this phenotype, we generated osteoblast‐specific Mdm2 overexpressing (Mdm2TgOb) mice in 2 different strains, C57BL/6 and DBA. These mice did not develop malignancies; however, these animals and the MG63 human osteosarcoma cell line with high levels of Mdm2 showed an increase in bone mineralization. Importantly, overexpression of Mdm2 corrected age‐related bone loss in mice, providing a role for the proto‐oncogenic activity of Mdm2 in bone health of adult animals
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