Abstract: Bone remodeling is a continuous physiological process that requires constant generation of new osteoblasts from mesenchymal stem cells (MSCs). Differentiation of MSCs to osteoblast requires a metabolic switch from glycolysis to increased mitochondrial respiration to ensure the sufficient energy supply to complete this process. As a consequence of this increased mitochondrial metabolism, the levels of endogenous reactive oxygen species (ROS) rise. In the current study we analyzed the role of forkhead box O3 (FOXO3) in the control of ROS levels in human MSCs (hMSCs) during osteogenic differentiation. Treatment of hMSCs with H2O2 induced FOXO3 phosphorylation at Ser294 and nuclear translocation. This ROS-mediated activation of FOXO3 was dependent on mitogen-activated protein kinase 8 (MAPK8/JNK) activity. Upon FOXO3 downregulation, osteoblastic differentiation was impaired and hMSCs lost their ability to control elevated ROS levels. Our results also demonstrate that in response to elevated ROS levels, FOXO3 induces autophagy in hMSCs. In line with this, impairment of autophagy by autophagy-related 7 (ATG7) knockdown resulted in a reduced capacity of hMSCs to regulate elevated ROS levels, together with a reduced osteoblast differentiation. Taken together our findings are consistent with a model where in hMSCs, FOXO3 is required to induce autophagy and thereby reduce elevated ROS levels resulting from the increased mitochondrial respiration during osteoblast differentiation. These new molecular insights provide an important contribution to our better understanding of bone physiology. Resumen: La remodelación ósea es un proceso fisiológico continuo que demanda la generación constante de nuevos osteoblastos a partir de células madre mesenquimales (CMMs). La diferenciación de las CMMs a osteoblastos requiere un cambio de glicólisis a respiración mitocondrial para así asegurar la obtención de suficiente energía. Como consecuencia, los niveles endógenos de especies reactivas del oxígeno (ERO) se elevan siendo perjudiciales para la integridad celular. En el presente estudio hemos analizado el papel de FOXO3 en el control de ERO en las CMMs durante la diferenciación osteogénica. El tratamiento de las CMMs con H2O2 induce la fosforilacion de FOXO3 en la serina 294 resultando en la translocación de FOXO3 al núcleo. Dicha activación mediada por el aumento de ERO es dependiente de la actividad de JNK. Al disminuir los niveles de FOXO3, la diferenciación osteoblástica se deteriora y las CMMs pierden su capacidad para controlar los niveles de ERO. Adicionalmente, nuestros resultados demuestran que en presencia de ERO, FOXO3 induce la autofagia en CMMs. En este orden de ideas, la disminución en los niveles de ATG7 da lugar a una reducción de la capacidad de las CMMs para regular los niveles elevados de ERO, junto con una reducción de la diferenciación de osteoblastos. Tomados en conjunto, nuestros resultados son consistentes con un modelo en el que FOXO3 es necesario para inducir la autofagia y por lo tanto reducir los niveles elevados de ERO que resultan del aumento de la respiración mitocondrial durante la diferenciación de osteoblastos. Estos nuevos conocimientos moleculares son importantes para una mejor comprensión de la fisiología ósea.

Abstract: We investigate how to formalize reasoning that takes account of time by using connectives like “before” and “after.” We develop semantics for a formal logic, which we axiomatize. In proving that the axiomatization is strongly complete we show how a temporal ordering of propositions can yield a linear timeline. We formalize examples of ordinary language sentences to illustrate the scope and limitations of this method. We then discuss ways to deal with some of those limitations. Resumen: Investigamos sobre cómo al formalizar el razonamiento se puede tener el cuenta el tiempo al usar conectivos de tiempo tales como « antes » y « después ». Nosotros desarrollamos la semantica para un sistema formal, el cal podemos axiomatizar. Al probar la axiomatización es fuertemente completo mostramos cómo un orden temporal de prosiciones pueden dejar un tiempo lineal. Formalizamos algunos ejemplos de las frases del lenguaje natural para ilustrar el alcance y las limitaciones de este métodos. Nosotros discutiremos entonces cómo lidiar con dichas limitaciones.

Incisive interpretations of urban-forest sustainability are important in furthering our understanding of how to sustain the myriad values associated with urban forests. Our analysis of earlier interpretations reveals conceptual gaps. These interpretations are attached to restrictive definitions of a sustainable urban forest and limited to a rather mechanical view of maintaining the biophysical structure of trees. The probing of three conceptual domains (urban forest concepts, sustainable development, and sustainable forest management) leads to a broader interpretation of urban-forest sustainability as the process of sustaining urban forest values through time and across space. We propose that values—and not services, benefits, functions or goods—is a superior concept to refer to what is to be sustained in and by an urban forest.

This article examines the existing arguments of the Democratic Peace Theory on why democracies do not fight each other. It aims to summarize the most important aspects of the theory, and to provide adequate counterarguments. First, it explains the general implications of the theory, including its origins and explanations. Second, it explores the related critiques and controversies. Third, it identifies the theory’s practical application. Finally, it offers conclusions on how effective this theory could be during the present days.

The purpose of my research is to identify the legal actions and/or administrative mechanisms established by the Colombian regulation that seek the prevention of the so-called orphan environmental damages caused by the exploration and exploitation of minerals by illegal miners within the territory. Moreover, I will determine whether or not landowners should be responsible for the environmental damage caused by illegal miners, in the case where they do not denounce the illegal activities occurring on their property to the government. In other words, the idea is to review the current regulation, and determine whether landowners should be responsible for the activities caused by third parties (illegal miners) on their properties, and if so, which legal actions should be filed by landowners in order to avoid responsibility in those cases. Hence, I will review which special duties landowners may have with respect to illegal mining on their properties, and which legal actions they should file before competent governmental authorities in order to inform them of these illegal activities. This would have the purpose of helping the government to stop the illegal activities by having the information about where these activities are being carried out, and therefore, prevent the appearance of new environmental damages. By this point, it may be clear that denouncing illegal activities is just a small part of the solution. In order to stop illegal mining it would be also necessary to reflect on the current environmental, social, economical, and cultural policies, strategies and programs. However, the law might contribute to find out a plausible solution. Notwithstanding the above, it is important to point out that I will focus my research only on the identification of the different legal actions, and not on their application and enforcement. Hence, the questions that I will try to resolve will be: (i) whether or not landowners have any special duty of denouncing the illegal mining activities that might take place on their properties (based on the ecological function of the property constitutional principle) (ii) which are the available legal actions and administrative mechanisms under Colombian regulation that should be used by a landowner in order to avoid responsibility and prevent orphan environmental damages caused by the performance of illegal mining activities on their property. I will however not analyze the application of these actions on a day-to-day basis; I will address some of the concerns with respect to the current system.

Transcriptional activity of Forkhead box transcription factor class O (FOXO) proteins can result in a variety of cellular outcomes depending on cell type and activating stimulus. These transcription factors are negatively regulated by the phosphoinositol 3-kinase (PI3K)–protein kinase B (PKB) signaling pathway, which is thought to have a pivotal role in regulating survival of tumor cells in a variety of cancers. Recently, it has become clear that FOXO proteins can promote resistance to anti-cancer therapeutics, designed to inhibit PI3K–PKB activity, by inducing the expression of proteins that provide feedback at different levels of this pathway. We questioned whether such a feedback mechanism may also exist directly at the level of FOXO-induced transcription. To identify critical modulators of FOXO transcriptional output, we performed gene expression analyses after conditional activation of key components of the PI3K–PKB–FOXO signaling pathway and identified FOXP1 as a direct FOXO transcriptional target. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that FOXP1 binds enhancers that are pre-occupied by FOXO3. By sequencing the transcriptomes of cells in which FOXO is specifically activated in the absence of FOXP1, we demonstrate that FOXP1 can modulate the expression of a specific subset of FOXO target genes, including inhibiting expression of the pro-apoptotic gene BIK. FOXO activation in FOXP1-knockdown cells resulted in increased cell death, demonstrating that FOXP1 prevents FOXO-induced apoptosis. We therefore propose that FOXP1 represents an important modulator of FOXO-induced transcription, promoting cellular survival.

Incorporating different kinds of micro-theories of cognition and modulating several mechanisms to unify all the recommended actions and outputs of an Intelligent System when a huge amount of environmental variables are changing continuously with increasing complexity, may become a very comprehensive task. The presented framework proposes an Hybrid Cognitive Architecture that relies on integrating of emergent systems approaches —connectionist and autopoietic systems—, and cognitivist approaches, in order to combine implicit and explicit processes necessary in developing cognitive skills. The proposed architecture includes different kinds of learning capabilities at each cognitive level which grant to the architecture a big plasticity. In addition, the propounded attention module includes an evolutionary mechanism based on gene expression programming to evolve a set of eligibility conditions in charge of modulating the coalition/ subordination of specialized behaviours, taking into consideration the theatre metaphor for consciousness. Finally, a co-evolutionary mechanism is proposed to propagate behaviours and knowledge between cognitive systems —Agents— on the basis of memetic engineering. The proposed architecture was proved in an animat environment using a multi-agent platform where several emergent properties of self-organization arose.

The Colombian composition, “Caimaré” (1949), by Luis Uribe Bueno (1916-2000) is a rare example of music written for saxophone and orchestra in Latin America. This piece reaches a particular importance in the repertoire for saxophone and orchestra because not only does it open a window into Colombian musical culture at the time, but it also presents a conciliation of the diverse musical elements that represented national identity of Colombia at that time. Additionally, the piece also raises some unsettling questions: Why did Luis Uribe Bueno compose music for saxophone and orchestra when the saxophone is an uncommon instrument in classical music and even more so in Andean Colombian music? Why did he write the piece? For whom? Was Caimaré just an isolated example, or were there other similar pieces? What were the music-cultural influences? In this paper, I will survey key aspects of Caimaré and its relationship to thehistory, composition, and performance of saxophone music in Colombia. I will show how the saxophone played a predominant role in the popular music of the Atlantic coastal region, as opposed to its relative rarity in the classical music tradition and in Andean folkloric contexts. My study will explore the role of the saxophone in one of the most representative tropical bands in Colombian music, Lucho Bermudez' s orchestra, and the influence that orchestra had on Uribe Bueno’s composition. Finally, this study will illustrate how Uribe Bueno combined traditional Spanish rhythms from the pasodoble and Caribbean influences from the Cuban bolero within the traditional Colombian pasillo in his representation of national music identity.

Bogotá is facing the problem of a large and rapidly growth to its periphery, reducing green areas, affecting the environment and stressing the city’s infrastructure just to name some negative effects. This scenario is even worse when looking to the city centre in which many buildings are abandoned or not used to their full potential. Other buildings need an intervention in order to meet current legislation and activities requirements. Environmental architecture seems not to be part of the agenda. In the other hand, many of the new buildings are not aware of how the design can affect the quality of the space and the environmental performance of the building. Glazed facades facing all orientations, equal treatment to all facades, lack of solar control elements, heating and cooling in a climate where sometimes coupling with the outside is desirable are just some of the things that suggest a review of what is being done.

Miel I, a Roller Compact Concrete (RCC) dam located in Colombia, has operated for almost ten years and operational/commercial practices and hydrological behavior has been stable. However, during the last two years, Miel I has confront changes in these two aspects. Before these changes, Miel I spillway was used just in two occasions and during a short period of time. However, because these changes, the spillway was used during 30 days in 2010 and 47 days in 2011. Additionally, since August 2010, the reservoir has increased its tributaries due to the Guarino tunnel diverse project. All these aspects have changed the reservoir levels during all the year and especially during raining season and affected directly the dam behavior. Miel I has confront forces and solicitudes which was never exposed. As a product of this, small fissures and changes in some instrumentation levels were observed during this time. It is clear that these changes have not compromised the dam safety although, it is also true that the Miel I dam for first time in ten years has been request to work against reservoir highest levels. The information, analysis and conclusions collected during these periods of time will allow the maintenance group to define, in advance, practices for this new condition and more important, will close the gap between the operational practices and the dam safety standards.