Cellular processes associated with LRRK2 function and dysfunction.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) encoding gene are the most common cause of monogenic Parkinson's Disease (PD). The identification of LRRK2 polymorphisms associated with increased risk for sporadic PD, as well as the observation that LRRK2-PD has an almost indistinguishable pathological phenotype from the sporadic form of disease, suggested LRRK2 as the culprit to provide understanding for both familial and sporadic PD cases. LRRK2 is a large protein with both GTPase and kinase functions. Mutations segregating with PD reside within the enzymatic core of LRRK2, suggesting the modification of its activity greatly impacts disease onset and progression. Although progress has been gained since its discovery in 2004, there is still much to be understood regarding LRRK2's physiological and neurotoxic properties. Unsurprisingly, given the presence of multiple enzymatic domains, LRRK2 has been associated with a diverse set of cellular functions and signalling pathways including mitochondrial function, vesicle trafficking together with endocytosis, retromer complex modulation and autophagy. This review will discuss the state of current knowledge for the role of LRRK2 in health and disease with discussion of potential substrates of phosphorylation and functional partners with particular emphasis on signalling mechanisms. As well, the use of immune cells in LRRK2 research and the role of oxidative stress as a regulator of LRRK2 activity and cellular function shall also be discussed. This article is protected by copyright. All rights reserved

Search for H → ττ in production processes in association with jets in CMS

A search for a light Higgs boson in the di-τ final state has been performed in CMS. Results, based on the 2011 data analysis and on an integrated luminosity corresponding to 4.6 fb−1 are presented and discussed along with the experimental issues related to the reconstruction of events in associated production processes

Relativistic Tunneling Through Two Successive Barriers

We study the relativistic quantum mechanical problem of a Dirac particle tunneling through two successive electrostatic barriers. Our aim is to study the emergence of the so-called \emph{Generalized Hartman Effect}, an effect observed in the context of nonrelativistic tunneling as well as in its electromagnetic counterparts, and which is often associated with the possibility of superluminal velocities in the tunneling process. We discuss the behavior of both the phase (or group) tunneling time and the dwell time, and show that in the limit of opaque barriers the relativistic theory also allows the emergence of the Generalized Hartman Effect. We compare our results with the nonrelativistic ones and discuss their interpretation.Comment: 7 pages, 3 figures. Revised version, with a new appendix added. Slightly changes in the styles and captions of Figures 1 and 2. To appear in Physical Review

A Deep Learning approach to Reduced Order Modelling of Parameter Dependent Partial Differential Equations

Within the framework of parameter dependent PDEs, we develop a constructive approach based on Deep Neural Networks for the efficient approximation of the parameter-to-solution map. The research is motivated by the limitations and drawbacks of state-of-the-art algorithms, such as the Reduced Basis method, when addressing problems that show a slow decay in the Kolmogorov n-width. Our work is based on the use of deep autoencoders, which we employ for encoding and decoding a high fidelity approximation of the solution manifold. In order to fully exploit the approximation capabilities of neural networks, we consider a nonlinear version of the Kolmogorov n-width over which we base the concept of a minimal latent dimension. We show that this minimal dimension is intimately related to the topological properties of the solution manifold, and we provide some theoretical results with particular emphasis on second order elliptic PDEs. Finally, we report numerical experiments where we compare the proposed approach with classical POD-Galerkin reduced order models. In particular, we consider parametrized advection-diffusion PDEs, and we test the methodology in the presence of strong transport fields, singular terms and stochastic coefficients

Legacy Network Integration with SDN-IP Implementation towards a Multi-Domain SoDIP6 Network Environment

[EN] The logical separation of the data plane and the control plane of the network device conceptually defined by software-defined networking (SDN) creates many opportunities to create smart networking with better efficiency for network management and operation. SDN implementation over telecommunications (Telcos) and Internet service provider (ISP) networks is a challenging issue due to the lack of a high maturity level of SDN-based standards and several other critical factors that are considered during the real-time migration of existing legacy IPv4 networks. Different migration approaches have been studied; however, none of them seem to be close to realizing implementation. This paper implements the SDN-IP and Open Network Operating System (ONOS) SDN controller to migrate legacy IPv4 networks to multi-domain software-defined IPv6 (SoDIP6) networks and experimentally evaluate the viability of joint network migration in the ISP networks. We present results using extensive simulations for the suitable placement of the master ONOS controller during network migration by considering minimum control path latency using optimal path routing and the breadth first router replacement (BFR) technique. Our empirical analysis and evaluations show that the identification of the median router to attach the master controller and router migration planning using BFR give better results for carrier-grade legacy networks' migration to SoDIP6 networks.This research was partially funded by the Norwegian University of Science and Technology, Trondhiem, Norway (NTNU) under Sustainable Engineering Education Project (SEEP) financed by EnPE, University Grant Commission (grant-ID: FRG7475Engg01), Bhaktapur, Nepal, Nepal academy of Science and Technology (NAST), Kathmandu, Nepal, and U.S. National Science Foundation (NSF). The work of Danda B. Rawat was partly supported by the U.S. National Science Foundation (NSF) under grants CNS 1650831 and HRD 1828811. Any opinions, findings, and conclusions or recommendations expressed in this article are those of the authors and should not be interpreted as necessarily representing the official policies, either expressed or implied, of the NSF. We are thankful to the ERASMUS+ KA107 project and the GRC lab team members at Universitat Politècnica De València for the research support and facilitation.Dawadi, BR.; Rawat, DB.; Joshi, SR.; Manzoni, P. (2020). Legacy Network Integration with SDN-IP Implementation towards a Multi-Domain SoDIP6 Network Environment. Electronics. 9(9):1-22. https://doi.org/10.3390/electronics9091454S12299Dawadi, B. R., Rawat, D. B., & Joshi, S. R. (2019). Software Defined IPv6 Network: A New Paradigm for Future Networking. Journal of the Institute of Engineering, 15(2), 1-13. doi:10.3126/jie.v15i2.27636Dawadi, B. R., Rawat, D. B., Joshi, S. R., & Manzoni, P. (2020). Evolutionary gaming approach for decision making of Tier‐3 Internet service provider networks migration to SoDIP6 networks. International Journal of Communication Systems, 33(11). doi:10.1002/dac.4399Gu, D., Su, J., Xue, Y., Wang, D., Li, J., Luo, Z., & Yan, B. (2020). Modeling IPv6 adoption from biological evolution. Computer Communications, 158, 166-177. doi:10.1016/j.comcom.2020.02.081IPv6 Capability Measurement https://stats.labs.apnic.net/ipv6Dawadi, B. R., Rawat, D. B., Joshi, S. R., & Keitsch, M. M. (2018). Joint Cost Estimation Approach for Service Provider Legacy Network Migration to Unified Software Defined IPv6 Network. 2018 IEEE 4th International Conference on Collaboration and Internet Computing (CIC). doi:10.1109/cic.2018.00056Csikor, L., Szalay, M., Retvari, G., Pongracz, G., Pezaros, D. P., & Toka, L. (2020). Transition to SDN is HARMLESS: Hybrid Architecture for Migrating Legacy Ethernet Switches to SDN. IEEE/ACM Transactions on Networking, 28(1), 275-288. doi:10.1109/tnet.2019.2958762Sandhya, Sinha, Y., & Haribabu, K. (2017). A survey: Hybrid SDN. Journal of Network and Computer Applications, 100, 35-55. doi:10.1016/j.jnca.2017.10.003Mostafaei, H., Lospoto, G., Di Lallo, R., Rimondini, M., & Di Battista, G. (2020). A framework for multi‐provider virtual private networks in software‐defined federated networks. International Journal of Network Management, 30(6). doi:10.1002/nem.2116Dawadi, B. R., Rawat, D. B., & Joshi, S. R. (2019). Evolutionary Dynamics of Service Provider Legacy Network Migration to Software Defined IPv6 Network. Advances in Intelligent Systems and Computing, 245-257. doi:10.1007/978-3-030-19861-9_24Salsano, S., Ventre, P. L., Lombardo, F., Siracusano, G., Gerola, M., Salvadori, E., … Prete, L. (2016). Hybrid IP/SDN Networking: Open Implementation and Experiment Management Tools. IEEE Transactions on Network and Service Management, 13(1), 138-153. doi:10.1109/tnsm.2015.2507622Vissicchio, S., Tilmans, O., Vanbever, L., & Rexford, J. (2015). Central Control Over Distributed Routing. Proceedings of the 2015 ACM Conference on Special Interest Group on Data Communication. doi:10.1145/2785956.2787497Rizvi, S. N., Raumer, D., Wohlfart, F., & Carle, G. (2015). Towards carrier grade SDNs. Computer Networks, 92, 218-226. doi:10.1016/j.comnet.2015.09.029Risdianto, A. C., Tsai, P.-W., Ling, T. C., Yang, C.-S., & Kim, J. (2017). Enhanced Onos Sdn Controllers Deployment For Federated Multi-Domain Sdn-Cloud With Sd-Routing-Exchange. Malaysian Journal of Computer Science, 30(2), 134-153. doi:10.22452/mjcs.vol30no2.5Ventre, P. L., Salsano, S., Gerola, M., Salvadori, E., Usman, M., Buscaglione, S., … Snow, W. (2017). SDN-Based IP and Layer 2 Services with an Open Networking Operating System in the GÉANT Service Provider Network. IEEE Communications Magazine, 55(4), 71-79. doi:10.1109/mcom.2017.1600194SDN-IP Arhitecture https://wiki.onosproject.org/display/ONOS/SDN-IP+ArchitectureLee, H.-L., Liu, T.-L., & Chen, M. (2019). Deploying SDN-IP over Transnational Network Testbed. 2019 IEEE International Conference on Consumer Electronics - Taiwan (ICCE-TW). doi:10.1109/icce-tw46550.2019.8991776Das, T., Sridharan, V., & Gurusamy, M. (2020). A Survey on Controller Placement in SDN. IEEE Communications Surveys & Tutorials, 22(1), 472-503. doi:10.1109/comst.2019.2935453Chen, W., Chen, C., Jiang, X., & Liu, L. (2018). Multi-Controller Placement Towards SDN Based on Louvain Heuristic Algorithm. IEEE Access, 6, 49486-49497. doi:10.1109/access.2018.2867931Qi, Y., Wang, D., Yao, W., Li, H., & Cao, Y. (2019). Towards Multi-Controller Placement for SDN Based on Density Peaks Clustering. ICC 2019 - 2019 IEEE International Conference on Communications (ICC). doi:10.1109/icc.2019.8761814Lu, J., Zhang, Z., Hu, T., Yi, P., & Lan, J. (2019). A Survey of Controller Placement Problem in Software-Defined Networking. IEEE Access, 7, 24290-24307. doi:10.1109/access.2019.2893283Singh, A. K., Maurya, S., Kumar, N., & Srivastava, S. (2019). Heuristic approaches for the reliable SDN controller placement problem. Transactions on Emerging Telecommunications Technologies, 31(2). doi:10.1002/ett.3761Das, T., & Gurusamy, M. (2018). Resilient Controller Placement in Hybrid SDN/Legacy Networks. 2018 IEEE Global Communications Conference (GLOBECOM). doi:10.1109/glocom.2018.8647566Heller, B., Sherwood, R., & McKeown, N. (2012). The controller placement problem. ACM SIGCOMM Computer Communication Review, 42(4), 473-478. doi:10.1145/2377677.2377767SDN Control Plane Performance: Raising the Bar on SDN Performance, Scalability, and High Availability https://wiki.onosproject.org/download/attachments/13994369/Whitepaper-%20ONOS%20Kingfisher%20release%20performance.pdf?version=

Wide-range optical spin orientation in Ge from near-infrared to visible light

Ge-based spin-photodiodes have been employed to investigate the spectral dependence of optical spin orientation in germanium, in the range 400-1550 nm. We found the expected maximum in the spin polarization of photocarriers for excitation at the direct gap in Γ (1550 nm) and a second sizable peak due to photogeneration in the L valleys (530 nm). Data suggest distinct spin depolarization mechanisms for excitation at Γ and L, with shorter spin relaxation times whether the X point is involved. These devices can be used as integrated photon-helicity detectors over a wide spectral range

Migration cost optimization for service provider legacy network migration to software-defined IPv6 network

This is the peer reviewed version of the following article: Dawadi, BR, Rawat, DB, Joshi, SR, Manzoni, P, Keitsch, MM. Migration cost optimization for service provider legacy network migration to software-defined IPv6 network. Int J Network Mgmt. 2021; 31:e2145, which has been published in final form at https://doi.org/10.1002/nem.2145. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] This paper studies a problem for seamless migration of legacy networks of Internet service providers to a software-defined networking (SDN)-based architecture along with the transition to the full adoption of the Internet protocol version 6 (IPv6) connectivity. Migration of currently running legacy IPv4 networks into such new approaches requires either upgrades or replacement of existing networking devices and technologies that are actively operating. The joint migration to SDN and IPv6 network is considered to be vital in terms of migration cost optimization, skilled human resource management, and other critical factors. In this work, we first present the approaches of SDN and IPv6 migration in service providers' networks. Then, we present the common concerns of IPv6 and SDN migration with joint transition strategies so that the cost associated with joint migration is minimized to lower than that of the individual migration. For the incremental adoption of software-defined IPv6 (SoDIP6) network with optimum migration cost, a greedy algorithm is proposed based on optimal path and the customer priority. Simulation and empirical analysis show that a unified transition planning to SoDIP6 network results in lower migration cost.U.S. National Science Foundation (NSF), Grant/Award Number: CNS 1650831 and HRD 1828811; ERASMUS+ KA107; Nepal Academy of Science and Technology (NAST); Norwegian University of Science and Technology; University Grant Commission (UGC), Nepal, Grant/Award Number: FRG/74_75/Engg-1Dawadi, BR.; Rawat, DB.; Joshi, SR.; Manzoni, P.; Keitsch, MM. (2021). Migration cost optimization for service provider legacy network migration to software-defined IPv6 network. International Journal of Network Management. 31(4):1-24. https://doi.org/10.1002/nem.2145S124314APNIC.IPv6 capability measurement.https://stats.labs.apnic.net/ipv6. Accessed April 22 2020.Google Incl. IPv6 user access status.https://www.google.com/intl/en/ipv6/statistics.html. Accessed February 16 2020.Rawat, D. B., & Reddy, S. R. (2017). 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Journal of the Institute of Engineering, 15(2), 1-13. doi:10.3126/jie.v15i2.27636Shah, J. L., Bhat, H. F., & Khan, A. I. (2019). Towards IPv6 Migration and Challenges. International Journal of Technology Diffusion, 10(2), 83-96. doi:10.4018/ijtd.2019040105Rojas, E., Doriguzzi-Corin, R., Tamurejo, S., Beato, A., Schwabe, A., Phemius, K., & Guerrero, C. (2018). Are We Ready to Drive Software-Defined Networks? A Comprehensive Survey on Management Tools and Techniques. ACM Computing Surveys, 51(2), 1-35. doi:10.1145/3165290Contreras, L. M., Doolan, P., Lønsethagen, H., & López, D. R. (2015). Operational, organizational and business challenges for network operators in the context of SDN and NFV. Computer Networks, 92, 211-217. doi:10.1016/j.comnet.2015.07.016Amin, R., Reisslein, M., & Shah, N. (2018). Hybrid SDN Networks: A Survey of Existing Approaches. 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Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice

Cocaine methiodide (CM), a charged cocaine analog, cannot pass the blood brain barrier. It has been assumed the effects of systemic CM represent cocaine actions in peripheral tissues. However, the IC50 values of CM have not been clearly determined for the major cocaine targets: dopamine, norepinephrine, and serotonin transporters, and sodium channels. Using cells transfected with individual transporters from mice and synaptosomes from mouse striatum tissues, we observed that the inhibition IC50 values for monoamine uptake by CM were 31-fold to 184-fold higher compared to cocaine at each of the transporters. In dorsal root ganglion neurons, cocaine inhibited sodium channels with an apparent IC50 of 75 µM, while CM showed no observable effect at concentrations up to 3 mM. These results indicate that an equal dose of CM will not produce an equivalent peripheral effect of cocaine