POSENS: a practical open source solution for end-to-end network slicing

Network slicing represents a new paradigm to operate mobile networks. With network slicing, the underlying infrastructure is "sliced" into logically separate networks which can be customized to the specific needs of their tenant. Hand-on experiments on this technology are essential to understand its benefits and limits, and to validate the design and deployment choices. While some network slicing prototypes have been built for the radio access networks (RANs), leveraging on the wide availability of radio hardware and open source software, there is currently no open source suite for end-to-end network slicing available to the research community. In this paper we fill this gap by developing an end-to-end network slicing protocol stack, POSENS, which relies on a slice-aware shared RAN solution. We design the required algorithms and protocols, and provide a full implementation leveraging on state-of-the-art software components. We validate the effectiveness of POSENS in achieving tenant isolation and network slices customization, showing that no price in performance is paid to this end. We believe that our tool will prove very useful to researchers and practitioners working on this novel architectural paradigm.This work has been performed in the framework of the H2020-ICT-2014-2 project 5G NORMA (Grant Agreement No. 671584) and within the 5G-MoNArch project, part of the Phase II of the 5th Generation Public Private Partnership (5G-PPP) program partially funded by the European Commission within the Horizon 2020 Framework Program

SEMPER: a stateless traffic engineering solution for WAN based on MP-TCP

Proceeding of: IEEE International Conference on Communications (ICC 2018)Enterprise Networking has a strong set of requirements in terms of resiliency, reliability and resources usage. With current approaches being based on monolithic and expensive infrastructures using dedicated overlay links, providers are moving to more economical hybrid solutions that encompass private dedicated links with public/regular Internet connections. However, these usually rely on complex, hardware-dependent and/or proprietary Traffic Engineering (TE) solutions, which are computationally costly, in particular for the forwarding nodes. In this paper, we propose SEMPER: a lightweight TE solution based on MP-TCP that, in contrast to other TE solutions, moves the complexity to the endpoints of the connection, and relieves the forwarding elements from complex operations or even maintaining state. As our evaluation shows, SEMPER efficiently makes use of all available paths between the endpoints while maintaining fairness, and properly adapts to variations on the available capacity.This work has been partly supported by the H2020 5GMoNArch project (grant agreement 761445), and by the Madrid Regional Government through the TIGRE5-CM program (S2013/ICE-2919)

Nuberu : Reliable RAN Virtualization in Shared Platforms

RAN virtualization will become a key technology for the last mile of next-generation mobile networks driven by initiatives such as the O-RAN alliance. However, due to the computing fluctuations inherent to wireless dynamics and resource contention in shared computing infrastructure, the price to migrate from dedicated to shared platforms may be too high. Indeed, we show in this paper that the baseline architecture of a base station¿s distributed unit (DU) collapses upon moments of deficit in computing capacity. Recent solutions to accelerate some signal processing tasks certainly help but do not tackle the core problem: a DU pipeline that requires predictable computing to provide carrier-grade reliability. We present Nuberu, a novel pipeline architecture for 4G/5G DUs specifically engineered for non-deterministic computing platforms. Our design has one key objective to attain reliability: to guarantee a minimum set of signals that preserve synchronization between the DU and its users during computing capacity shortages and, provided this, maximize network throughput. To this end, we use techniques such as tight deadline control, jitter-absorbing buffers, predictive HARQ, and congestion control. Using an experimental prototype, we show that Nuberu attains 95% of the theoretical spectrum efficiency in hostile environments, where state-of-art approaches lose connectivity, and at least 80% resource savingsWe would like to thank our shepherd and reviewers for their valuable comments and feedback. This work has been supported by the European Commission through Grant No. 101017109 (DAEMON project) and Grant No. 101015956 (Hexa-X project), and the CERCA Programme/Generalitat de Catalunya

Demo: Nuberu - A Reliable DU DesignSuitable for Virtualization Platforms

We demonstrate Nuberu. The scenario consists of a DU under test (DuT), and one or more DUs sharing computing resources. A dashboard lets us control the type of DuT: Baseline, implemented with vanilla srsRAN, or Nuberu; the number of competing vDUs; and their SNR. A second screen shows real-time metrics: the processing latency of the TBs from each vDU instance; the throughput performance of DuT; the processing latency of DU jobs from DuT; and the ratio of latency constraint violations of DuT jobs. We show how the throughput attained by the baseline DU approach collapses upon sufficiently high computing interference from the competing DUs. Conversely, we show that the DU design introduced in [3] preserves reliability irrespective of the computing interference.This work has been supported by the EC through Grant No. 101017109 (DAEMON) and Grant No. 856709 (5Growth)

On the benefits of bringing cloud-awareness to network virtual functions

Proceeding of: 2018 European Conference on Networks and Communications (EuCNC), June 18-21, Ljubljana, SloveniaWe are currently observing the softwarization of communication networks, where network functions are translated from monolithic pieces of equipment to programs running over a shared pool of computational, storage, and communication resources. As the amount of this resources might vary over time, in this paper we discuss the potential benefits of introducing resource awareness to softwarized network functions. More specifically, we focus on the case of computational elasticity, namely, the ability to endure shortages of computational resources while providing an adequate (although non-ideal) service. We discuss how to enable this ability by re-designing network functions, and illustrate the potential benefits of this approach with a numerical evaluation

Imbalance of p75(NTR)/TrkB protein expression in Huntington's disease: implication for neuroprotective therapies

Neuroprotective therapies based on brain-derived neurotrophic factor (BDNF) administration have been proposed forHuntington's disease (HD) treatment. However, our group has recently reported reduced levels of TrkB in HD mouse models andHD human brain suggesting that besides a decrease on BDNF levels a reduction of TrkB expression could also contribute todiminished neurotrophic support in HD. BDNF can also bind to p75 neurotrophin receptor (p75NTR) modulating TrkB signaling.Therefore, in this study we have analyzed the levels of p75NTRin several HD models, as well as in HD human brain. Our datademonstrates a p75NTR/TrkB imbalance in the striatum of two different HD mouse models,HdhQ111/111homozygous knockin miceand R6/1 mice that was also manifested in the putamen of HD patients. The imbalance between TrkB and p75NTRlevels in a HDcellular model did not affect BDNF-mediated TrkB activation of prosurvival pathways but induced activation of apoptoticcascades as demonstrated by increased JNK phosphorylation. Moreover, BDNF failed to protect mutant huntingtin striatal cellstransfected with p75NTRagainst NMDA-mediated excitotoxicity, which was associated with decreased Akt phosphorylation.Interestingly, lack of Akt activation following BDNF and NMDA treatment correlated with increased PP1 levels. Accordingly,pharmacological inhibition of PP1 by okadaic acid (OA) prevented mutant huntingtin striatal cell death induced by NMDA andBDNF. Altogether, our findings demonstrate that the p75NTR/TrkB imbalance induced by mutant huntingtin in striatal cellsassociated with the aberrant activity of PP1 disturbs BDNF neuroprotection likely contributing to increasing striatal vulnerabilityin HD. On the basis of this data we hypothesize that normalization of p75NTRand/or TrkB expression or their signaling willimprove BDNF neuroprotective therapies in HD

PKM2 subcellular localization is involved in oxaliplatin resistance acquisition in HT29 human colorectal cancer cell lines

Ajuts: Beca bianual de la Fundació Olga Torres 2008-2009Chemoresistance is the main cause of treatment failure in advanced colorectal cancer (CRC). However, molecular mechanisms underlying this phenomenon remain to be elucidated. In a previous work we identified low levels of PKM2 as a putative oxaliplatin-resistance marker in HT29 CRC cell lines and also in patients. In order to assess how PKM2 influences oxaliplatin response in CRC cells, we silenced PKM2 using specific siRNAs in HT29, SW480 and HCT116 cells. MTT test demonstrated that PKM2 silencing induced resistance in HT29 and SW480 cells and sensitivity in HCT116 cells. Same experiments in isogenic HCT116 p53 null cells and double silencing of p53 and PKM2 in HT29 cells failed to show an influence of p53. By using trypan blue stain and FITC-Annexin V/PI tests we detected that PKM2 knockdown was associated with an increase in cell viability but not with a decrease in apoptosis activation in HT29 cells. Fluorescence microscopy revealed PKM2 nuclear translocation in response to oxaliplatin in HCT116 and HT29 cells but not in OXA-resistant HTOXAR3 cells. Finally, by using a qPCR Array we demonstrated that oxaliplatin and PKM2 silencing altered cell death gene expression patterns including those of BMF, which was significantly increased in HT29 cells in response to oxaliplatin, in a dose and time-dependent manner, but not in siPKM2-HT29 and HTOXAR3 cells. BMF gene silencing in HT29 cells lead to a decrease in oxaliplatin-induced cell death. In conclusion, our data report new non-glycolytic roles of PKM2 in response to genotoxic damage and proposes BMF as a possible target gene of PKM2 to be involved in oxaliplatin response and resistance in CRC cells

Pyk2 in the amygdala modulates chronic stress sequelae via PSD-95-related micro-structural changes

Major depressive disorder (MDD) is a common disorder with a variety of symptoms including mood alterations, anhedonia, sleep and appetite disorders, and cognitive disturbances. Stressful life events are among the strongest risk factors for developing MDD. At the cellular level, chronic stress results in the modification of dendritic spine morphology and density. Here, we study the role of Pyk2 in the development of depressive-like symptoms induced by a model of chronic unpredictable mild stress (CUMS). Pyk2 is a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the forebrain principal neurons and involved in spine structure and density regulation. We show that Pyk2 knockout mice are less affected to anxiety-like and anhedonia-like phenotypes induced by the CUMS paradigm. Using region-specific knockout, we demonstrate that this phenotype is fully recapitulated by selective Pyk2 inactivation in the amygdala. We also show that in the absence of Pyk2 the spine alterations, PSD-95 clustering, and NMDA receptors changes induced by the CUMS paradigm are prevented. Our results reveal a possible role for Pyk2 in the response to stress and in synaptic markers expression and spine density regulation in the amygdala. We suggest that Pyk2 contributes to stress-induced responses through micro-structural changes and that its deficit may contribute to the resilience to chronic stress

Cyclin-Dependent Kinase 5 Dysfunction Contributes to Depressive-like Behaviors in Huntington's Disease by Altering the DARPP-32 Phosphorylation Status in the Nucleus Accumbens

Background: Depression is the most common psychiatric condition in Huntington's disease (HD), with rates more than twice those found in the general population. At the present time, there is no established molecular evidence to use as a basis for depression treatment in HD. Indeed, in some patients, classic antidepressant drugs exacerbate chorea or anxiety. Cyclin-dependent kinase 5 (Cdk5) has been involved in processes associated with anxiety and depression. This study evaluated the involvement of Cdk5 in the development and prevalence of depressive-like behaviors in HD and aimed to validate Cdk5 as a target for depression treatment. Methods: We evaluated the impact of pharmacological inhibition of Cdk5 in depressive-like and anxiety-like behaviors in Hdh+/Q111 knock-in mutant mice by using a battery of behavioral tests. Biochemical and morphological studies were performed to define the molecular mechanisms acting downstream of Cdk5 activation. A double huntingtin/DARPP-32 (dopamine- and cAMP-regulated phosphoprotein 32) knock-in mutant mouse was generated to analyze the role of DARPP-32 in HD depression. Results: We found that Hdh+/Q111 mutant mice exhibited depressive-like, but not anxiety-like, behaviors starting at 2 months of age. Cdk5 inhibition by roscovitine infusion prevented depressive-like behavior and reduced DARPP-32 phosphorylation at Thr75 in the nucleus accumbens. Hdh+/Q111 mice heterozygous for DARPP-32 Thr75Ala point mutation were resistant to depressive-like behaviors. We identified β-adducin phosphorylation as a Cdk5 downstream mechanism potentially mediating structural spine plasticity changes in the nucleus accumbens and depressive-like behavior. Conclusions: These results point to Cdk5 in the nucleus accumbens as a critical contributor to depressive-like behaviors in HD mice by altering DARPP-32/β-adducin signaling and disrupting the dendritic spine cytoskeleton

Altered m6A RNA methylation contributes to hippocampal memory deficits in Huntington's disease mice.

N6-methyladenosine (m6A) regulates many aspects of RNA metabolism and is involved in learning and memory processes. Yet, the impact of a dysregulation of post-transcriptional m6A editing on synaptic impairments in neurodegenerative disorders remains unknown. Here we investigated the m6A methylation pattern in the hippocampus of Huntington's disease (HD) mice and the potential role of the m6A RNA modification in HD cognitive symptomatology. m6A modifications were evaluated in HD mice subjected to a hippocampal cognitive training task through m6A immunoprecipitation sequencing (MeRIP-seq) and the relative levels of m6A-modifying proteins (FTO and METTL14) by subcellular fractionation and Western blot analysis. Stereotaxic CA1 hippocampal delivery of AAV-shFTO was performed to investigate the effect of RNA m6A dysregulation in HD memory deficits. Our results reveal a m6A hypermethylation in relevant HD and synaptic related genes in the hippocampal transcriptome of Hdh+/Q111 mice. Conversely, m6A is aberrantly regulated in an experience-dependent manner in the HD hippocampus leading to demethylation of important components of synapse organization. Notably, the levels of RNA demethylase (FTO) and methyltransferase (METTL14) were modulated after training in the hippocampus of WT mice but not in Hdh+/Q111 mice. Finally, inhibition of FTO expression in the hippocampal CA1 region restored memory disturbances in symptomatic Hdh+/Q111 mice. Altogether, our results suggest that a differential RNA methylation landscape contributes to HD cognitive symptoms and uncover a role of m6A as a novel hallmark of HD