The Armc10/SVH gene: Genome context, regulation of mitochondrial dynamics and protection against Aß-induced mitochondrial fragmentation

Mitochondrial function and dynamics are essential for neurotransmission, neural function and neuronal viability. Recently, we showed that the eutherian-specific Armcx gene cluster (Armcx1-6 genes), located in the X chromosome, encodes for a new family of proteins that localise to mitochondria, regulating mitochondrial trafficking. The Armcx gene cluster evolved by retrotransposition of the Armc10 gene mRNA, which is present in all vertebrates and is considered to be the ancestor gene. Here we investigate the genomic organisation, mitochondrial functions and putative neuroprotective role of the Armc10 ancestor gene. The genomic context of the Armc10 locus shows considerable syntenic conservation among vertebrates, and sequence comparisons and CHIP-data suggest the presence of at least three conserved enhancers. We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain. Furthermore, we show that Armc10 levels regulate mitochondrial trafficking in neurons, but not mitochondrial aggregation, by controlling the number of moving mitochondria. We further demonstrate that the Armc10 protein interacts with the KIF5/Miro1-2/Trak2 trafficking complex. Finally, we show that overexpression of Armc10 in neurons prevents Aß-induced mitochondrial fission and neuronal death. Our data suggest both conserved and differential roles of the Armc10/Armcx gene family in regulating mitochondrial dynamics in neurons, and underscore a protective effect of the Armc10 gene against Aß-induced toxicity. Overall, our findings support a further degree of regulation of mitochondrial dynamics in the brain of more evolved mammals. © 2014 Macmillan Publishers Limited All rights reserved.This project was supported by grants BFU2008-3980 and SAF2011-13232-E (Acciones Complementarias) (MINECO, Spain) to ES, by grant BFU2010-21507 to FU, by grant SAF2011-23550 to RT, by grant ‘BFU2011-23921’ and the ICREA Academia Prize (Generalitat de Catalunya) to JGF, and by a grant from the CIBERNED. SM and EN hold FPI fellowshipsPeer Reviewe

La normativa jurídica de la O.I.T. en materia de libertad y su incidencia en el sindicalismo español

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Derecho, leída en 1974.Fac. de DerechoTRUEProQuestpu

La normativa jurídica de la O.I.T. en materia de libertad y su incidencia en el sindicalismo español

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Derecho, leída en 1974.Fac. de DerechoTRUEProQuestpu

Slicing with guaranteed quality of service in wifi networks

Network slicing has recently been proposed as one of the main enablers for 5G networks. The slicing concept consists of the partition of a physical network into several self-contained logical networks (slices) that can be tailored to offer different functional or performance requirements. In the context of 5G networks, we argue that existing ubiquitous WiFi technology can be exploited to cope with new requirements. Therefore, in this paper, we propose a novel mechanism to implement network slicing in WiFi Access Points. We formulate the resource allocation problem to the different slices as a stochastic optimization problem, where each slice can have bit rate, delay, and capacity requirements. We devise a solution to the problem above using the Lyapunov drift optimization theory, and we develop a novel queuing and scheduling algorithm. We have used MATLAB and Simulink to build a prototype of the proposed solution, whose performance has been evaluated in a typical slicing scenario.This work has been supported in part by the European Commission and the Spanish Government (Fondo Europeo de Desarrollo Regional, FEDER) by means of the EU H2020 NECOS (777067) and ADVICE (TEC2015-71329) projects, respectivel

Providing reliable services over wireless networks using a low overhead random linear coding scheme

In this work, we propose a novel intra-flow network coding solution, which is based on the combination of a low overhead Random Linear Coding (RLC) scheme and UDP, to offer a reliable communication service. In the initial protocol specification, the required overhead could be rather large and this had an impact over the observed performance. We therefore include an improvement to reduce such overhead, by decreasing the header length. We describe an analytical model that can be used to assess the performance of the proposed scheme. We also use an implementation within the ns-3 framework to assess the correctness of this model and to broaden the analysis, considering different performance indicators and more complex network topologies. In all cases, the proposed solution clearly outperforms a more traditional approach, in which the TCP protocol is used as a means to offer a reliable communication service.This work has been supported by the Spanish Government by its funding through the project COSAIF, “Connectivity as a Service: Access for the Internet of the Future” (TEC2012-38754-C02-01)

Guaranteed bit rate slicing in WiFi networks

In forthcoming 5G networks, slicing has been proposed as a means to partition a shared physical network infrastructure into different self-contained logical parts (slices), which are set up to satisfy certain requirements. Although the topic has been thoroughly investigated by the scientific community and the industry, there are not many works addressing the challenges that appear when trying to exploit slicing techniques over WiFi networks. In this paper, we propose a novel method of allocating resources for WiFi networks to satisfy minimum bit rate requirements. We formulate an optimization problem, and we propose a solution based on the theory of Lyapunov drift optimization. The validity of the proposed solution is assessed by means of a simulation-based evaluation in Matlab.This work has been supported in part by the European Commission and the Spanish Government (Fondo Europeo de Desarrollo Regional, FEDER) by means of the EU H2020 NECOS (777067) and ADVICE (TEC2015-71329) projects, respectively

Fast and efficient energy-oriented cell assignment in heterogeneous networks

The cell assignment problem is combinatorial, with increased complexity when it is tackled considering resource allocation. This paper models joint cell assignment and resource allocation for cellular heterogeneous networks, and formalizes cell assignment as an optimization problem. Exact algorithms can find optimal solutions to the cell assignment problem, but their execution time increases drastically with realistic network deployments. In turn, heuristics are able to find solutions in reasonable execution times, but they get usually stuck in local optima, thus failing to find optimal solutions. Metaheuristic approaches have been successful in finding solutions closer to the optimum one to combinatorial problems for large instances. In this paper we propose a fast and efficient heuristic that yields very competitive cell assignment solutions compared to those obtained with three of the most widely-used metaheuristics, which are known to find solutions close to the optimum due to the nature of their search space exploration. Our heuristic approach adds energy expenditure reduction in its algorithmic design. Through simulation and formal statistical analysis, the proposed scheme has been proved to produce efficient assignments in terms of the number of served users, resource allocation and energy savings, while being an order of magnitude faster than metaheuritsic-based approaches.This paper has been supported by the National Council of Research and Technology (CONACYT) through Grant FONCICYT/272278 and the ERANetLAC (Network of the European Union, Latin America, and the Caribbean Countries) Project ELAC2015/T100761. This paper is partially supported also by the ADVICE Project, TEC2015-71329 (MINECO/FEDER) and the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 777067 (NECOS Project)

Joint route selection and split level management for 5G C-RAN

This work tackles the problem faced by network/infrastructure providers of jointly selecting routing and functional split level to satisfy requests from virtual mobile network operators (vMNOs). We build a novel system model that brings together all the involved elements and features, embracing split levels defined by the 3GPP and packet switch fronthaul network. To our best knowledge, this is the first work that provides a solution for multiple vMNO requests considering the two aforementioned sub-problems (i.e. split selection and routing). We use the model defined to formulate an optimization problem, which is characterized by the exponential size of its search space. We propose two heuristic approaches to address this problem: (1) a greedy scheme, and (2) an evolutionary algorithm, which is also improved with a specialized initialization. We conduct extensive experiments to assess the performance and behavior of the proposed methods, over varying network instances. When possible, we also perform comparisons with respect to the optimal solution and a well-known commercial solver. Our results indicate that the proposed techniques represent appropriate trade-offs between solution quality and execution time, and can serve complementary goals: the quality of the results yielded by our evolutionary method are better, but at the cost of longer execution times; in contrast, our greedy algorithm offers a reasonably appropriate performance, with an execution time that is notably lower. Our experiments show that it is possible to produce near-optimal results to the above complex problem through computationally efficient algorithmic solutions.This paper has been partially supported by the Secretary of Public Education of Mexico (SEP) and Cinvestav through research grant 262, and the National Council of Research and Technology (CONACYT) through grant ERANetLACFONCICYT No. 272278. Luis Diez and Ramon Agüero acknowledge the funding by the Spanish Government (Ministerio de Economía y Competitividad, Fondo Europeo de Desarrollo Regional, MINECO-FEDER) by means of the project FIERCE: Future Internet Enabled Resilient smart CitiEs (RTI2018-093475-AI00)

Slicing in WiFi networks through airtime-based resource allocation

Network slicing is one of the key enabling technologies for 5G networks. It allows infrastructure owners to assign resources to service providers (tenants), which will afterwards use them to satisfy their end-user demands. This paradigm, which changes the way networks have been traditionally managed, was initially proposed in the wired realm (core networks). More recently, the scientific community has paid attention to the integration of network slicing in wireless cellular technologies (LTE). However, there are not many works addressing the challenges that appear when trying to exploit slicing techniques over WiFi networks, in spite of their growing relevance. In this paper we propose a novel method of proportionally distributing resources in WiFi networks, by means of the airtime. We develop an analytical model, which shed light on how such resources could be split. The validity of the proposed model is assessed by means of simulation-based evaluation over the ns-3 framework.This work has been supported in part by the European Commission and the Spanish Government (Fondo Europeo de desarrollo Regional, FEDER) by means of the EU H2020 NECOS (777067) and ADVICE (TEC2015-71329) projects, respectively

Silibinin Suppresses Tumor Cell-Intrinsic Resistance to Nintedanib and Enhances Its Clinical Activity in Lung Cancer

The anti-angiogenic agent nintedanib has been shown to prolong overall and progression-free survival in patients with advanced non-small-cell lung cancer (NSCLC) who progress after first-line platinum-based chemotherapy and second-line immunotherapy. Here, we explored the molecular basis and the clinical benefit of incorporating the STAT3 inhibitor silibinin-a flavonolignan extracted from milk thistle-into nintedanib-based schedules in advanced NSCLC. First, we assessed the nature of the tumoricidal interaction between nintedanib and silibinin and the underlying relevance of STAT3 activation in a panel of human NSCLC cell lines. NSCLC cells with poorer cytotoxic responses to nintedanib exhibited a persistent, nintedanib-unresponsive activated STAT3 state, and deactivation by co-treatment with silibinin promoted synergistic cytotoxicity. Second, we tested whether silibinin could impact the lysosomal sequestration of nintedanib, a lung cancer cell-intrinsic mechanism of nintedanib resistance. Silibinin partially, but significantly, reduced the massive lysosomal entrapment of nintedanib occurring in nintedanib-refractory NSCLC cells, augmenting the ability of nintedanib to reach its intracellular targets. Third, we conducted a retrospective, observational multicenter study to determine the efficacy of incorporating an oral nutraceutical product containing silibinin in patients with NSCLC receiving a nintedanib/docetaxel combination in second- and further-line settings (n = 59). Overall response rate, defined as the combined rates of complete and partial responses, was significantly higher in the study cohort receiving silibinin supplementation (55%) than in the control cohort (22%, p = 0.011). Silibinin therapy was associated with a significantly longer time to treatment failure in multivariate analysis (hazard ratio 0.43, p = 0.013), despite the lack of overall survival benefit (hazard ratio 0.63, p = 0.190). Molecular mechanisms dictating the cancer cell-intrinsic responsiveness to nintedanib, such as STAT3 activation and lysosomal trapping, are amenable to pharmacological intervention with silibinin. A prospective, powered clinical trial is warranted to confirm the clinical relevance of these findings in patients with advanced NSCLC