Efficiency vs. Stability in a Mixed Network Formation Model

Documentos de Trabajo

4th European Conference on Energy Efficiency and Sustainability in Architecture and Planning : Donostia-San Sebastián, 1-3 Julio 2013

XXXII Cursos de Verano de la UPV/EHU

5th European Conference on Energy Efficiency and Sustainability in Architecture and Planning : Donostia-San Sebastián, 7-9 Julio 2014

XXXIII Cursos de Verano de la UPV/EHU

6th European Conference on Energy Efficiency and Sustainability in Architecture and Planning

[ES]Esta obra recoge las comunicaciones seleccionadas para el 6º Congreso Europeo sobre Eficiencia Energética y Sostenibilidad en Arquitectura, organizado por el grupo de investigación Calidad de Vida en Arquitectura de la Universidad del País Vasco/Euskal Herriko Unibertsitatea. El congreso, que se celebra en el marco de los XXXIV Cursos de Verano de la UPV/EHU, aborda en esta cuarta edición el tema “Ciudades en riesgo: resiliencia y redundancia”. Alrededor de este tema general se desarrollan cinco ponencias magistrales, a cargo de Margaretha Breil (Centro Euro-Mediterráneo para el Cambio Climático), Cristina Garzillo Leemhuis (ICLEI), Ignasi Fontanals (OptiCits), Juan Carlos Barrios Montenegro (Global Action Plan) y Manuel Valdés López (Ajuntament de Barcelona). Además, 24 comunicaciones seleccionadas por el comité científico presentarán trabajos de investigaciones actuales en las sesiones orales y póster. Es objetivo paralelo del congreso es fortalecer las líneas de investigación en eficiencia energética y sostenibilidad de los grupos de investigación y formación de la UPV/ EHU comprometidos con esta propuesta, con objeto de colaborar en el reforzamiento de la I D i en su ámbito de conocimiento y apoyar la apuesta específica de los Gobiernos Central y Vasco, así como de otras instituciones nacionales e internacionales respecto a las actividades de I D i en las materias relacionadas con el cambio climático, la eficiencia energética y la sostenibilidad ambiental [ENG] This work contains the selected abstracts of the 6th European Conference on Energy Efficiency and Sustainability in Architecture and Planning, organized by the research group Quality of life in Architecture of the University of the Basque Country. The conference is part of the XXXIV Summer Courses of the UPV/EHU and deals, in its fourth edition, with the topic “Cities at risk: resilience and redundancy”. Around this general theme there are five invited speakers: Margaretha Breil (Euro-Mediterranean Centre for Climate Change), Cristina Garzillo Leemhuis (ICLEI), Ignasi Fontanals (OptiCits), Juan Carlos Barrios Montenegro (Global Action Plan) y Manuel Valdés López (Barcelona City Council). 24 abstracts additional have been selected by the scientific committee that offer actual research works in presentations and posters. The purpose of the conferences is to strengthen the investigation lines in energy efficiency and sustainability of the research and education groups of the University of the Basque Country (UPV/EHU) involved, with the purpose of collaborating in the reinforcement of the I D i in its field of knowledge, and support the specific projects of the Central and Basque Governments, as well as other national and international institutions related to the I Di activities in similar fields of climate change, energy efficiency and environmental sustainability.

Improving Content Delivery Efficiency through Multi-Layer Mobile Edge Adaptation

This paper presents a novel architecture for optimizing the HTTP-based multimedia delivery in multi-user mobile networks. This proposal combines the usual client-driven dynamic adaptation scheme DASH-3GPP with network-assisted adaptation capabilities, in order to maximize the overall Quality of Experience. The foundation of this combined adaptation scheme is based on two state of the art technologies. On one hand, adaptive HTTP streaming with multi-layer encoding allows efficient media delivery and improves the experienced media quality in highly dynamic channels. Additionally, it enables the possibility to implement network-level adaptations for better coping with multi-user scenarios. On the other hand, mobile edge computing facilitates the deployment of mobile services close to the user. This approach brings new possibilities in modern and future mobile networks, such as close to zero delays and awareness of the radio status. The proposal in this paper introduces a novel element, denoted as Mobile Edge-DASH Adaptation Function, which combines all these advantages to support efficient media delivery in mobile multi-user scenarios. Furthermore, we evaluate the performance enhancements of this content- and user context-aware scheme through simulations of a mobile multimedia scenario.

Apaf-1 Inhibitors Protect from Unwanted Cell Death in In Vivo Models of Kidney Ischemia and Chemotherapy Induced Ototoxicity

Background: Excessive apoptosis induces unwanted cell death and promotes pathological conditions. Drug discovery efforts aimed at decreasing apoptotic damage initially targeted the inhibition of effector caspases. Although such inhibitors were effective, safety problems led to slow pharmacological development. Therefore, apoptosis inhibition is still considered an unmet medical need. Methodology and Principal Findings: The interaction between Apaf-1 and the inhibitors was confirmed by NMR. Target specificity was evaluated in cellular models by siRNa based approaches. Cell recovery was confirmed by MTT, clonogenicity and flow cytometry assays. The efficiency of the compounds as antiapoptotic agents was tested in cellular and in vivo models of protection upon cisplatin induced ototoxicity in a zebrafish model and from hypoxia and reperfusion kidney damage in a rat model of hot ischemia. Conclusions: Apaf-1 inhibitors decreased Cytc release and apoptosome-mediated activation of procaspase-9 preventing cell and tissue damage in ex vivo experiments and in vivo animal models of apoptotic damage. Our results provide evidence that Apaf-1 pharmacological inhibition has therapeutic potential for the treatment of apoptosis-related diseases.

Leukemia-Associated Mutations in Nucleophosmin Alter Recognition by CRM1: Molecular Basis of Aberrant Transport

Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein, normally enriched in nucleoli, that performs several activities related to cell growth. NPM mutations are characteristic of a subtype of acute myeloid leukemia (AML), where mutant NPM seems to play an oncogenic role. AML-associated NPM mutants exhibit altered subcellular traffic, being aberrantly located in the cytoplasm of leukoblasts. Exacerbated export of AML variants of NPM is mediated by the nuclear export receptor CRM1, and due, in part, to a mutationally acquired novel nuclear export signal (NES). To gain insight on the molecular basis of NPM transport in physiological and pathological conditions, we have evaluated the export efficiency of NPM in cells, and present new data indicating that, in normal conditions, wild type NPM is weakly exported by CRM1. On the other hand, we have found that AML-associated NPM mutants efficiently form complexes with CRM1HA (a mutant CRM1 with higher affinity for NESs), and we have quantitatively analyzed CRM1HA interaction with the NES motifs of these mutants, using fluorescence anisotropy and isothermal titration calorimetry. We have observed that the affinity of CRM1HA for these NESs is similar, which may help to explain the transport properties of the mutants. We also describe NPM recognition by the import machinery. Our combined cellular and biophysical studies shed further light on the determinants of NPM traffic, and how it is dramatically altered by AML-related mutations.

Lipid Nanoparticles as Carriers for RNAi against Viral Infections: Current Status and Future Perspectives

The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.

Effects of Spring Temperatures on the Strength of Selection on Timing of Reproduction in a Long-Distance Migratory Bird

Climate change has differentially affected the timing of seasonal events for interacting trophic levels, and this has often led to increased selection on seasonal timing. Yet, the environmental variables driving this selection have rarely been identified, limiting our ability to predict future ecological impacts of climate change. Using a dataset spanning 31 years from a natural population of pied flycatchers (Ficedula hypoleuca), we show that directional selection on timing of reproduction intensified in the first two decades (1980-2000) but weakened during the last decade (2001-2010). Against expectation, this pattern could not be explained by the temporal variation in the phenological mismatch with food abundance. We therefore explored an alternative hypothesis that selection on timing was affected by conditions individuals experience when arriving in spring at the breeding grounds: arriving early in cold conditions may reduce survival. First, we show that in female recruits, spring arrival date in the first breeding year correlates positively with hatch date; hence, early-hatched individuals experience colder conditions at arrival than late-hatched individuals. Second, we show that when temperatures at arrival in the recruitment year were high, early-hatched young had a higher recruitment probability than when temperatures were low. We interpret this as a potential cost of arriving early in colder years, and climate warming may have reduced this cost. We thus show that higher temperatures in the arrival year of recruits were associated with stronger selection for early reproduction in the years these birds were born. As arrival temperatures in the beginning of the study increased, but recently declined again, directional selection on timing of reproduction showed a nonlinear change. We demonstrate that environmental conditions with a lag of up to two years can alter selection on phenological traits in natural populations, something that has important implications for our understanding of how climate can alter patterns of selection in natural populations.

Structure-function analysis of USP1: insights into the role of Ser313 phosphorylation site and the effect of cancer-associated mutations on autocleavage

Background: In complex with its cofactor UAF1, the USP1 deubiquitinase plays an important role in cellular processes related to cancer, including the response to DNA damage. The USP1/UAF1 complex is emerging as a novel target in cancer therapy, but several aspects of its function and regulation remain to be further clarified. These include the role of the serine 313 phosphorylation site, the relative contribution of different USP1 sequence motifs to UAF1 binding, and the potential effect of cancer-associated mutations on USP1 regulation by autocleavage. Methods: We have generated a large set of USP1 structural variants, including a catalytically inactive form (C90S), non-phosphorylatable (S313A) and phosphomimetic (S313D) mutants, deletion mutants lacking potential UAF1 binding sites, a mutant (GG/AA) unable to undergo autocleavage at the well-characterized G670/G671 diglycine motif, and four USP1 mutants identified in tumor samples that cluster around this cleavage site (G667A, L669P, K673T and A676T). Using cell-based assays, we have determined the ability of these mutants to bind UAF1, to reverse DNA damage-induced monoubiquitination of PCNA, and to undergo autocleavage. Results: A non-phosphorylatable S313A mutant of USP1 retained the ability to bind UAF1 and to reverse PCNA ubiquitination in cell-based assays. Regardless of the presence of a phosphomimetic S313D mutation, deletion of USP1 fragment 420-520 disrupted UAF1 binding, as determined using a nuclear relocation assay. The UAF1 binding site in a second UAF1-interacting DUB, USP46, was mapped to a region homologous to USP1(420-520). Regarding USP1 autocleavage, co-expression of the C90S and GG/AA mutants did not result in cleavage, while the cancer-associated mutation L669P was found to reduce cleavage efficiency. Conclusions: USP1 phosphorylation at S313 is not critical for PCNA deubiquitination, neither for binding to UAF1 in a cellular environment. In this context, USP1 amino acid motif 420-520 is necessary and sufficient for UAF1 binding. This motif, and a homologous amino acid segment that mediates USP46 binding to UAF1, map to the Fingers sub-domain of these DUBs. On the other hand, our results support the view that USP1 autocleavage may occur in cis, and can be altered by a cancer-associated mutation.

Self-reported sitting time and physical activity: interactive associations with mental well-being and productivity in office employees

Background: Little is known about how sitting time, alone or in combination with markers of physical activity (PA), influences mental well-being and work productivity. Given the need to develop workplace PA interventions that target employees' health related efficiency outcomes; this study examined the associations between self-reported sitting time, PA, mental well-being and work productivity in office employees. Methods: Descriptive cross-sectional study. Spanish university office employees (n = 557) completed a survey measuring socio-demographics, total and domain specific (work and travel) self-reported sitting time, PA (International Physical Activity Questionnaire short version), mental well-being (Warwick-Edinburg Mental Well-Being Scale) and work productivity (Work Limitations Questionnaire). Multivariate linear regression analyses determined associations between the main variables adjusted for gender, age, body mass index and occupation. PA levels (low, moderate and high) were introduced into the model to examine interactive associations. Results: Higher volumes of PA were related to higher mental well-being, work productivity and spending less time sitting at work, throughout the working day and travelling during the week, including the weekends (p < 0.05). Greater levels of sitting during weekends was associated with lower mental well-being (p < 0.05). Similarly, more sitting while travelling at weekends was linked to lower work productivity (p < 0.05). In highly active employees, higher sitting times on work days and occupational sitting were associated with decreased mental well-being (p < 0.05). Higher sitting times while travelling on weekend days was also linked to lower work productivity in the highly active (p < 0.05). No significant associations were observed in low active employees. Conclusions: Employees' PA levels exerts different influences on the associations between sitting time, mental well-being and work productivity. The specific associations and the broad sweep of evidence in the current study suggest that workplace PA strategies to improve the mental well-being and productivity of all employees should focus on reducing sitting time alongside efforts to increase PA.