Delivering Live Multimedia Streams to Mobile Hosts in a Wireless Internet with Multiple Content Aggregators

We consider the distribution of channels of live multimedia content (e.g., radio or TV broadcasts) via multiple content aggregators. In our work, an aggregator receives channels from content sources and redistributes them to a potentially large number of mobile hosts. Each aggregator can offer a channel in various configurations to cater for different wireless links, mobile hosts, and user preferences. As a result, a mobile host can generally choose from different configurations of the same channel offered by multiple alternative aggregators, which may be available through different interfaces (e.g., in a hotspot). A mobile host may need to handoff to another aggregator once it receives a channel. To prevent service disruption, a mobile host may for instance need to handoff to another aggregator when it leaves the subnets that make up its current aggregator�s service area (e.g., a hotspot or a cellular network).\ud In this paper, we present the design of a system that enables (multi-homed) mobile hosts to seamlessly handoff from one aggregator to another so that they can continue to receive a channel wherever they go. We concentrate on handoffs between aggregators as a result of a mobile host crossing a subnet boundary. As part of the system, we discuss a lightweight application-level protocol that enables mobile hosts to select the aggregator that provides the �best� configuration of a channel. The protocol comes into play when a mobile host begins to receive a channel and when it crosses a subnet boundary while receiving the channel. We show how our protocol can be implemented using the standard IETF session control and description protocols SIP and SDP. The implementation combines SIP and SDP�s offer-answer model in a novel way

Increasing the Transparency, Accountability and Controllability of multi-domain networks with the UPIN framework

Demands for a more trustworthy Internet are constantly increasing, in particular to support emerging critical services such as intelligent urban transport systems and smart energy grids. Such cyber-physical systems require more insight into the properties of network operators (e.g., in terms of the security posture of their equipment) and more control over which network operators transport their data, thus going well beyond the traditional security paradigm which the Internet security community currently focuses on (confidentiality, availability, and integrity). In this work-in-progress paper we propose the UPIN framework, which aims to fulfill these new trust requirements. The framework advances the state-of-the-art by defining components needed to incorporate transparency, accountability, and controllability into the Internet or other types of inter-domain networks. The framework is based on our analysis of a smart grid use case to understand the specific needs of critical service providers and a literature study on existing technologies. We also discuss our ongoing work, and the demands and challenges of implementing and deploying the UPIN framework

Inter-Destination Multimedia Synchronization; Schemes, Use Cases and Standardization

Traditionally, the media consumption model has been a passive and isolated activity. However, the advent of media streaming technologies, interactive social applications, and synchronous communications, as well as the convergence between these three developments, point to an evolution towards dynamic shared media experiences. In this new model, geographically distributed groups of consumers, independently of their location and the nature of their end-devices, can be immersed in a common virtual networked environment in which they can share multimedia services, interact and collaborate in real-time within the context of simultaneous media content consumption. In most of these multimedia services and applications, apart from the well-known intra and inter-stream synchronization techniques that are important inside the consumers playout devices, also the synchronization of the playout processes between several distributed receivers, known as multipoint, group or Inter-destination multimedia synchronization (IDMS), becomes essential. Due to the increasing popularity of social networking, this type of multimedia synchronization has gained in popularity in recent years. Although Social TV is perhaps the most prominent use case in which IDMS is useful, in this paper we present up to 19 use cases for IDMS, each one having its own synchronization requirements. Different approaches used in the (recent) past by researchers to achieve IDMS are described and compared. As further proof of the significance of IDMS nowadays, relevant organizations (such as ETSI TISPAN and IETF AVTCORE Group) efforts on IDMS standardization (in which authors have been and are participating actively), defining architectures and protocols, are summarized.This work has been financed, partially, by Universitat Politecnica de Valencia (UPV), under its R&D Support Program in PAID-05-11-002-331 Project and in PAID-01-10, and by TNO, under its Future Internet Use Research & Innovation Program. The authors also want to thank Kevin Gross for providing some of the use cases included in Sect. 1.2.Montagud, M.; Boronat Segui, F.; Stokking, H.; Van Brandenburg, R. (2012). Inter-Destination Multimedia Synchronization; Schemes, Use Cases and Standardization. Multimedia Systems. 18(6):459-482. https://doi.org/10.1007/s00530-012-0278-9S459482186Kernchen, R., Meissner, S., Moessner, K., Cesar, P., Vaishnavi, I., Boussard, M., Hesselman, C.: Intelligent multimedia presentation in ubiquitous multidevice scenarios. IEEE Multimedia 17(2), 52–63 (2010)Vaishnavi, I., Cesar, P., Bulterman, D., Friedrich, O., Gunkel, S., Geerts, D.: From IPTV to synchronous shared experiences challenges in design: distributed media synchronization. Signal Process Image Commun 26(7), 370–377 (2011)Geerts, D., Vaishnavi, I., Mekuria, R., Van Deventer, O., Cesar, P.: Are we in sync?: synchronization requirements for watching on-line video together, CHI ‘11, New York, USA (2011)Boronat, F., Lloret, J., García, M.: Multimedia group and inter-stream synchronization techniques: a comparative study. Inf. Syst. 34(1), 108–131 (2009)Chen, M.: A low-latency lip-synchronized videoconferencing system. In: SIGCHI Conference on Human Factors in Computing Systems, CHI’03, ACM, pp. 464–471, New York (2003)Ishibashi, Y., Tasaka, S., Ogawa, H.: Media synchronization quality of reactive control schemes. IEICE Trans. Commun. E86-B(10), 3103–3113 (2003)Ademoye, O.A., Ghinea, G.: Synchronization of olfaction-enhanced multimedia. IEEE Trans. Multimedia 11(3), 561–565 (2009)Cesar, P., Bulterman, D.C.A., Jansen, J., Geerts, D., Knoche, H., Seager, W.: Fragment, tag, enrich, and send: enhancing social sharing of video. ACM Trans. Multimedia Comput. Commun. Appl. 5(3), Article 19, 27 pages (2009)Van Deventer, M.O., Stokking, H., Niamut, O.A., Walraven, F.A., Klos, V.B.: Advanced Interactive Television Service Require Synchronization, IWSSIP 2008. Bratislava, June (2008)Premchaiswadi, W., Tungkasthan, A., Jongsawat, N.: Enhancing learning systems by using virtual interactive classrooms and web-based collaborative work. In: Proceedings of the IEEE Education Engineering Conference (EDUCON 2010), pp. 1531–1537. Madrid, Spain (2010)Diot, C., Gautier, L.: A distributed architecture for multiplayer interactive applications on the internet. IEEE Netw 13(4), 6–15 (1999)Mauve, M., Vogel, J., Hilt, V., Effelsberg, W.: Local-lag and timewarp: providing consistency for replicated continuous applications. IEEE Trans. Multimedia 6(1), 45–57 (2004)Hosoya, K., Ishibashi, Y., Sugawara, S., Psannis, K.E.: Group synchronization control considering difference of conversation roles. In: IEEE 13th International Symposium on Consumer Electronics, ISCE ‘09, pp. 948–952 (2009)Roccetti, M., Ferretti, S., Palazzi, C.: The brave new world of multiplayer online games: synchronization issues with smart solution. In: 11th IEEE Symposium on Object Oriented Real-Time Distributed Computing (ISORC), pp. 587–592 (2008)Ott, D.E., Mayer-Patel, K.: An open architecture for transport-level protocol coordination in distributed multimedia applications. ACM Trans. Multimedia Comput. Commun. Appl. 3(3), 17 (2007)Boronat, F., Montagud, M., Guerri, J.C.: Multimedia group synchronization approach for one-way cluster-to-cluster applications. In: IEEE 34th Conference on Local Computer Networks, LCN 2009, pp. 177–184, Zürich (2009)Boronat, F., Montagud, M., Vidal, V.: Smooth control of adaptive media playout to acquire IDMS in cluster-based applications. In: IEEE LCN 2011, pp. 617–625, Bonn (2011)Huang, Z., Wu, W., Nahrstedt, K., Rivas, R., Arefin, A.: SyncCast: synchronized dissemination in multi-site interactive 3D tele-immersion. In: Proceedings of MMSys, USA (2011)Kim, S.-J., Kuester, F., Kim, K.: A global timestamp-based approach for enhanced data consistency and fairness in collaborative virtual environments. ACM/Springer Multimedia Syst. J. 10(3), 220–229 (2005)Schooler, E.: Distributed music: a foray into networked performance. In: International Network Music Festival, Santa Monica, CA (1993)Miyashita, Y., Ishibashi, Y., Fukushima, N., Sugawara, S., Psannis K.E.: QoE assessment of group synchronization in networked chorus with voice and video. In: Proceedings of IEEE TENCON’11, pp. 393–397 (2011)Hesselman, C., Abbadessa, D., Van Der Beek, W., et al.: Sharing enriched multimedia experiences across heterogeneous network infrastructures. IEEE Commun. Mag. 48(6), 54–65 (2010)Montpetit, M., Klym, N., Mirlacher, T.: The future of IPTV—Connected, mobile, personal and social. Multimedia Tools Appl J 53(3), 519–532 (2011)Cesar, P., Bulterman, D.C.A., Jansen, J.: Leveraging the user impact: an architecture for secondary screens usage in an interactive television environment. ACM/Springer Multimedia Syst. 15(3), 127–142 (2009)Lukosch, S.: Transparent latecomer support for synchronous groupware. In: Proceedings of 9th International Workshop on Groupware (CRIWG), Grenoble, France, pp. 26–41 (2003)Steinmetz, R.: Human perception of jitter and media synchronization. IEEE J. Sel. Areas Commun. 14(1), 61–72 (1996)Stokking, H., Van Deventer, M.O., Niamut, O.A., Walraven, F.A., Mekuria, R.N.: IPTV inter-destination synchronization: a network-based approach, ICIN’2010, Berlin (2010)Mekuria, R.N.: Inter-destination media synchronization for TV broadcasts, Master Thesis, Faculty of Electrical Engineering, Mathematics and Computer Science, Department of Network architecture and Services, Delft University of Technology (2011)Pitt Ian, CS2511: Usability engineering lecture notes, localisation of sound sources. http://web.archive.org/web/20100410235208/http:/www.cs.ucc.ie/~ianp/CS2511/HAP.htmlNielsen, J.: Response times: the three important limits. http://www.useit.com/papers/responsetime.html (1994)ITU-T Rec G. 1010: End-User Multimedia QoS Categories. International Telecommunication Union, Geneva (2001)Biersack, E., Geyer, W.: Synchronized delivery and playout of distributed stored multimedia streams. ACM/Springer Multimedia Syst 7(1), 70–90 (1999)Xie, Y., Liu, C., Lee, M.J., Saadawi, T.N.: Adaptive multimedia synchronization in a teleconference system. ACM/Springer Multimedia Syst. 7(4), 326–337 (1999)Laoutaris, N., Stavrakakis, I.: Intrastream synchronization for continuous media streams: a survey of playout schedulers. IEEE Netw. Mag. 16(3), 30–40 (2002)Ishibashi, Y., Tsuji, A., Tasaka, S.: A group synchronization mechanism for stored media in multicast communications. In: Proceedings of the INFOCOM ‘97, Washington (1997)Ishibashi, Y., Tasaka, S.: A group synchronization mechanism for live media in multicast communications. IEEE GLOBECOM’97, pp. 746–752 (1997)Boronat, F., Guerri, J.C., Lloret, J.: An RTP/RTCP based approach for multimedia group and inter-stream synchronization. Multimedia Tools Appl. J. 40(2), 285–319 (2008)Ishibashi, I., Tasaka, S.: A distributed control scheme for group synchronization in multicast communications. In: Proceedings of International Symposium Communications, Kaohsiung, Taiwan, pp. 317–323 (1999)Lu, Y., Fallica, B., Kuipers, F.A., Kooij, R.E., Van Mieghem, P.: Assessing the quality of experience of SopCast. Int. J. Internet Protoc. Technol 4(1), 11–19 (2009)Shamma, D.A., Bastea-Forte, M., Joubert, N., Liu, Y.: Enhancing online personal connections through synchronized sharing of online video, ACM CHI’08 Extended Abstracts, Florence (2008)Ishibashi, Y., Tasaka, S.: A distributed control scheme for causality and media synchronization in networked multimedia games. In: Proceedings of 11th International Conference on Computer Communications and Networks, pp. 144–149, Miami, USA (2002)Ishibashi, Y., Tomaru, K., Tasaka, S., Inazumi, K.: Group synchronization in networked virtual environments. In: Proceedings of the 38th IEEE International Conference on Communications, pp. 885–890, Alaska, USA (2003)Tasaka, S., Ishibashi, Y., Hayashi, M.: Inter–destination synchronization quality in an integrated wired and wireless network with handover. IEEE GLOBECOM 2, 1560–1565 (2002)Kurokawa, Y., Ishibashi, Y., Asano, T.: Group synchronization control in a remote haptic drawing system. In: Proceedings of IEEE International Conference on Multimedia and Expo, pp. 572–575, Beijing, China (2007)Hashimoto, T., Ishibashi, Y.: Group Synchronization Control over Haptic Media in a Networked Real-Time Game with Collaborative Work, Netgames’06, Singapore (2006)Nunome, T., Tasaka, S.: Inter-destination synchronization quality in a multicast mobile ad hoc network. In: Proceedings of IEEE 16th International Symposium on Personal, Indoor and Mobile Radio Communications, pp. 1366–1370, Berlin, Germany (2005)Brandenburg, R., van Stokking, H., Van Deventer, M.O., Boronat, F., Montagud, M., Gross, K.: RTCP for inter-destination media synchronization, draft-brandenburg-avtcore-rtcp-for-idms-03.txt. In: IETF Audio/Video Transport Core Maintenance Working Group, Internet Draft, March 9 (2012)ETSI TS 181 016 V3.3.1 (2009-07) Telecommunications and Internet converged Services and Protocols for Advanced Networking (TISPAN); Service Layer Requirements to integrate NGN Services and IPTVETSI TS 182 027 V3.5.1 (2011-03) Telecommunications and Internet converged Services and Protocols for Advanced Networking (TISPAN); IPTV Architecture; IPTV functions supported by the IMS subsystemETSI TS 183 063 V3.5.2 (2011-03) Telecommunications and Internet converged Services and Protocols for Advanced Networking (TISPAN); IMS-based IPTV stage 3 specificationBrandenburg van, R., et al.: RTCP XR Block Type for inter-destination media synchronization, draft-brandenburg-avt-rtcp-for-idms-00.txt. In: IETF Audio/Video Transport Working Group, Internet Draft, Sept 24, 2010Williams, A., et al.: RTP Clock Source Signalling, draft-williams-avtcore-clksrc-00. In: IETF Audio/Video Transport Working Group, Internet Draft, February 28, 201

Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged acute lymphoblastic leukemia reveals a new therapeutic strategy

Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have a dismal prognosis. Survival outcomes have remained static in recent decades despite treatment intensification and novel therapies are urgently required. KMT2A-rearranged infant ALL cells are characterized by an abundance of promoter hypermethylation and exhibit high BCL-2 expression, highlighting potential for therapeutic targeting. Here, we show that hypomethylating agents exhibit in vitro additivity when combined with most conventional chemotherapeutic agents. However, in a subset of samples an antagonistic effect was seen between several agents. This was most evident when hypomethylating agents were combined with methotrexate, with upregulation of ATP-binding cassette transporters identified as a potential mechanism. Single agent treatment with azacitidine and decitabine significantly prolonged in vivo survival in KMT2A-rearranged infant ALL xenografts. Treatment of KMT2A-rearranged infant ALL cell lines with azacitidine and decitabine led to differential genome-wide DNA methylation, changes in gene expression and thermal proteome profiling revealed the target protein-binding landscape of these agents. The selective BCL-2 inhibitor, venetoclax, exhibited in vitro additivity in combination with hypomethylating or conventional chemotherapeutic agents. The addition of venetoclax to azacitidine resulted in a significant in vivo survival advantage indicating the therapeutic potential of this combination to improve outcome for infants with KMT2A-rearranged ALL

Trapping the HIV-1 V3 loop in a helical conformation enables broad neutralization

The third variable (V3) loop on the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein trimer is indispensable for virus cell entry. Conformational masking of V3 within the trimer allows efficient neutralization via V3 only by rare, broadly neutralizing glycan-dependent antibodies targeting the closed prefusion trimer but not by abundant antibodies that access the V3 crown on open trimers after CD4 attachment. Here, we report on a distinct category of V3-specific inhibitors based on designed ankyrin repeat protein (DARPin) technology that reinstitute the CD4-bound state as a key neutralization target with up to >90% breadth. Broadly neutralizing DARPins (bnDs) bound V3 solely on open envelope and recognized a four-turn amphipathic α-helix in the carboxy-terminal half of V3 (amino acids 314-324), which we termed 'αV3C'. The bnD contact surface on αV3C was as conserved as the CD4 binding site. Molecular dynamics and escape mutation analyses underscored the functional relevance of αV3C, highlighting the potential of αV3C-based inhibitors and, more generally, of postattachment inhibition of HIV-1