A novel system for glycosylation engineering by natural and artificial micrornas

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V-Edge: Virtual Edge Computing as an Enabler for Novel Microservices and Cooperative Computing

As we move from 5G to 6G, edge computing is one of the concepts that needs revisiting. Its core idea is still intriguing: instead of sending all data and tasks from an end user's device to the cloud, possibly covering thousands of kilometers and introducing delays that are just owed to limited propagation speed, edge servers deployed in close proximity to the user, e.g., at some 5G gNB, serve as proxy for the cloud. Yet this promising idea is hampered by the limited availability of such edge servers. In this paper, we discuss a way forward, namely the virtual edge computing (V-Edge) concept. V-Edge bridges the gap between cloud, edge, and fog by virtualizing all available resources including the end users' devices and making these resources widely available using well-defined interfaces. V-Edge also acts as an enabler for novel microservices as well as cooperative computing solutions. We introduce the general V-Edge architecture and we characterize some of the key research challenges to overcome, in order to enable wide-spread and even more powerful edge services

Quantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for CrossCohort Comparisons of COVID-19 Sera

The global coronavirus disease 2019 (COVID-19) pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent-phase plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous biosafety level 3 (BSL3) conditions, which limits high-throughput screening of patient and vaccine sera. Myriad BSL2-compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making intergroup comparisons difficult. To address these limitations, we developed a standardized VNA using CoV2-S pseudotyped particles (CoV2pp) based on vesicular stomatitis virus bearing the Renilla luciferase gene in place of its G glyco-protein (VSVDG); this assay can be robustly produced at scale and generate accurate neutralizing titers within 18 h postinfection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S enzyme-linked immunosorbent assay (ELISA) results and live-virus neutralizations in confirmed convalescent-patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n . 120). Our data (i) show that absolute 50% inhibitory concentration (absIC50), absIC80, and absIC90 values can be legitimately compared across diverse cohorts, (ii) highlight the substantial but consistent variability in neutralization potency across these cohorts, and (iii) support the use of the absIC80 as a more meaningful metric for assessing the neutralization potency of a vaccine or convalescent-phase sera. Lastly, we used our CoV2pp in a screen to identify ultrapermissive 293T clones that stably express ACE2 or ACE2 plus TMPRSS2. When these are used in combination with our CoV2pp, we can produce CoV2pp sufficient for 150,000 standardized VNAs/week. IMPORTANCE Vaccines and antibody-based therapeutics like convalescent-phase plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) are an essential part of determining vaccine or therapeutic efficacy. However, such efficacy testing is limited by the inherent dangers of working with the live virus, which requires specialized high-level biocontainment facilities. We there-fore developed a standardized replication-defective pseudotyped particle system that mimics the entry of live SARS-CoV-2. This tool allows for the safe and efficient measurement of NATs, determination of other forms of entry inhibition, and thorough investigation of virus entry mechanisms. Four independent labs across the globe validated our standardized VNA using diverse cohorts. We argue that a standardized and scalable assay is necessary for meaningful comparisons of the myriad of vaccines and antibody-based therapeutics becoming available. Our data provide generalizable metrics for assessing their efficacy.Fil: Oguntuyo, Kasopefoluwa. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Stevens, Christian S.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Hung, Chuan Tien. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ikegame, Satoshi. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Acklin, Joshua A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Kowdle, Shreyas S.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Carmichael, Jillian C.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Chiu, Hsin Ping. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Azarm, Kristopher D.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Haas, Griffin D.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Amanat, Fatima. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Klingler, Jéromine. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Baine, Ian. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Arinsburg, Suzanne. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Bandres, Juan C.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Siddiquey, Mohammed N. A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Schilke, Robert M.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Woolard, Matthew D.. State University of Louisiana; Estados UnidosFil: Zhang, Hongbo. State University of Louisiana; Estados UnidosFil: Duty, Andrew J.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Kraus, Thomas A.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Moran, Thomas M.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Tortorella, Domenico. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Lim, Jean K.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Hioe, Catarina E.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Zolla Pazner, Susan. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ivanov, Stanimir S.. State University of Louisiana; Estados UnidosFil: Kamil, Jeremy. State University of Louisiana; Estados UnidosFil: Krammer, Florian. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Lee, Benhur. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Ojeda, Diego Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: González López Ledesma, María Mora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Costa Navarro, Guadalupe Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Pallarés, H. M.. No especifíca;Fil: Sanchez, Lautaro Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Perez, P.. No especifíca;Fil: Ostrowsk, M.. No especifíca;Fil: Villordo, S. M.. No especifíca;Fil: Alvarez, D. E.. No especifíca;Fil: Caramelo, J. J.. No especifíca;Fil: Carradori, J.. No especifíca;Fil: Yanovsky, M. J.. No especifíca

Strain-Dependent Differences in Bone Development, Myeloid Hyperplasia, Morbidity and Mortality in Ptpn2-Deficient Mice

Single nucleotide polymorphisms in the gene encoding the protein tyrosine phosphatase TCPTP (encoded by PTPN2) have been linked with the development of autoimmunity. Here we have used Cre/LoxP recombination to generate Ptpn2ex2−/ex2− mice with a global deficiency in TCPTP on a C57BL/6 background and compared the phenotype of these mice to Ptpn2−/− mice (BALB/c-129SJ) generated previously by homologous recombination and backcrossed onto the BALB/c background. Ptpn2ex2−/ex2− mice exhibited growth retardation and a median survival of 32 days, as compared to 21 days for Ptpn2−/− (BALB/c) mice, but the overt signs of morbidity (hunched posture, piloerection, decreased mobility and diarrhoea) evident in Ptpn2−/− (BALB/c) mice were not detected in Ptpn2ex2−/ex2− mice. At 14 days of age, bone development was delayed in Ptpn2−/− (BALB/c) mice. This was associated with increased trabecular bone mass and decreased bone remodeling, a phenotype that was not evident in Ptpn2ex2−/ex2− mice. Ptpn2ex2−/ex2− mice had defects in erythropoiesis and B cell development as evident in Ptpn2−/− (BALB/c) mice, but not splenomegaly and did not exhibit an accumulation of myeloid cells in the spleen as seen in Ptpn2−/− (BALB/c) mice. Moreover, thymic atrophy, another feature of Ptpn2−/− (BALB/c) mice, was delayed in Ptpn2ex2−/ex2− mice and preceded by an increase in thymocyte positive selection and a concomitant increase in lymph node T cells. Backcrossing Ptpn2−/− (BALB/c) mice onto the C57BL/6 background largely recapitulated the phenotype of Ptpn2ex2−/ex2− mice. Taken together these results reaffirm TCPTP's important role in lymphocyte development and indicate that the effects on morbidity, mortality, bone development and the myeloid compartment are strain-dependent

Efficient wireless communication in vehicular networks

Die Verwendung von Funkkommunikation zum Austausch von Informationen zwischen Fahrzeugen, um die Sicherheit und Verkehrseffizienz zu erhöhen, hat sich als vorteilhaft erwiesen. In der Vergangenheit wurden dafür weltweit verschiedene Standards entworfen, z. B. ETSI ITS-G5 in Europa, oder IEEE 1609 WAVE in den USA; beide basieren auf IEEE 802.11p WLAN. Trotzdem stellt effiziente Kommunikation noch ein Problem für viele Anwendungen dar. Wir beginnen daher diese Dissertation mit einer analytischen Betrachtung der Leistungsfähigkeit von IEEE 802.11p. Als ersten Beitrag untersuchen wir die Effizienz von IEEE 802.11p basierter Unicast Kommunikation in hoch mobilen Szenarien. Diese Art der Übertragung wird in der ETSI ITS-G5 GeoNetworking Spezifikation als ein zentrales Kommunikationsparadigma verwendet. Unsere Ergebnisse zeigen, dass Unicast Kommunikation keinen Mehrwert in typischen Szenarien bietet und teils höhere Kommunikationslatenzen verursachen kann. Basierend auf diesen Ergebnissen und Einschränkungen des aktuellen ETSI ITS-G5 Standards entwickeln wir als zweiten Beitrag dieser Arbeit eine ausschließlich Broadcast basierte Netzwerkarchitektur, welche vier verschiedene Kommunikationsparadigmen unterstützt. Ein zentraler Bestandteil dieser Architektur ist die Verwendung von 2-hop-Nachbarschaftsinformationen mittels Bloom filter, um Fahrzeugen eine bessere Übersicht der Netzwerktopologie zu ermöglichen. In unserem dritten Beitrag werfen wir einen detaillierten Blick auf diese Nachbarschaften und entwickeln einen Algorithmus, um unabhängig der Straßentopologie 2-hop-Nachbarn zu informieren. Im Gegensatz zu herkömmlichen Ansätzen ohne Bloom filter können wir damit Kanallast einsparen und gleichzeitig die Anzahl der informierten Fahrzeuge erhöhen. Im vierten Beitrag dieser Arbeit widmen wir uns der Skalierbarkeit von ...Wireless communication among vehicles has been shown to be beneficial for a variety of use cases in the automotive domain ranging from pure safety to traffic efficiency and to entertainment applications. To accomplish communication, different protocol stacks have been standardized around the world, e.g., ETSI ITS-G5 in Europe and IEEE 1609 WAVE in the U.S., both building upon IEEE 802.11p WLAN, yet for many applications, efficiency is still a problem. We thus begin this PhD thesis with an analytical investigation of the capacity bounds of IEEE 802.11p. As a first contribution towards efficient wireless communication, we study the performance of IEEE 802.11p based unicast communication, which is, e.g., used by the ETSI ITS-G5 GeoNetworking specification. Our investigations reveal that unicast communication employing retransmissions at the MAC layer is not only not beneficial in vehicular communications, but maybe harmful in typical scenarios, as it leads to higher communication delays. Based on our findings and current limitations of ETSI ITS-G5, we present as a second contribution a purely broadcast based networking architecture, which categorizes communication demands of applications into four distinct classes. A central building block of our network layer is the support of 2-hop neighbor information using space efficient Bloom filters to provide nodes a better overview of their vicinity. In our third contribution, we take a detailed look on how to properly maintain this neighbor information and propose Bloom Hopping, a 2-hop message dissemination protocol, which operates independently from the road topology. Simulation results show that it can outperform traditional 2-hop approaches (not using Bloom filters) in terms of requiring less channel resources and providing better application performance. As a fourth contribution, we focus on the scalability of ...vorgelegt von Florian Klingler, angefertigt in der Fachgruppe Distributed Embedded Systems (CCS Labs) Heinz Nixdorf Institut Universität Paderborn ; Betreuer: Prof. Dr.-Ing. habil. Falko Dressler, Gutachter: Prof. Dr.-Ing. habil. Falko Dressler, Prof. Dr. Jiannong Cao, Prof. Dr.-Ing. Lars WolfTag der Verteidigung: 17.09.2018Der Promovend hat weitere Beteiligte angegebenUniversität Paderborn, Dissertation, 201

Adaptive Control Strategy for Stationary Electric Battery Storage Systems with Reliable Peak Load Limitation at Maximum Self-Consumption of Locally Generated Energy

Nowadays, stationary battery storage systems are generally used to optimize the self-consumption of electricity generated locally or to limit the peak load of the local grid connection. Self-consumption optimization aims to achieve economic benefits by using more of the self-generated electricity within the local grid. Batteries used for the optimization of self-consumption tend to present low states of charge and, therefore, normally do not contribute to peak load limitation. Peak load limitation is used to minimize the grid connection power to enable more cost-efficient grid connections. However, this function can only be achieved year-round if there is sufficient surplus electricity production or if the battery can be charged from the grid. In the latter case, the batteries are often fully charged and do not significantly optimize the self-consumption. This study presents a new operating strategy that combines all the advantages of the previous operating modes with none of the disadvantages. This can be accomplished by combining the operation modes depending on the particular situation, together with a variable battery charging process. Furthermore, a simulation-based optimization procedure is introduced for the optimal configuration of the parameters. The potential of this operating strategy is demonstrated based on application examples. As a result, the operating strategy enables reliable peak load limitation all year round while simultaneously optimizing self-consumption. The operating strategy can easily be adapted to meet changing requirements such as the increasing charging power demands of electric vehicles. Thanks to a simple process based on common measured variables, the operating strategy can be integrated smoothly into practical applications

Organoids for Modeling (Colorectal) Cancer in a Dish

Functional studies of primary cancer have been limited to animal models for a long time making it difficult to study aspects specific to human cancer biology. The development of organoid technology enabled us to culture human healthy and tumor cells as three-dimensional self-organizing structures in vitro for a prolonged time. Organoid cultures conserve the heterogeneity of the originating epithelium regarding cell types and tumor clonality. Therefore, organoids are considered an invaluable tool to study and genetically dissect various aspects of human cancer biology. In this review, we describe the applications, advantages, and limitations of organoids as human cancer models with the main emphasis on colorectal cancer

Dynamic Mobile Base Stations in 5G Networks - The Moving Network Paradigm

5G is the new generation of the global telecommunication network and is very important for Italy. For these reasons CNIT* decided to organize on December 3-5, 2019, the 5G-Italy event (https://www.5gitaly.eu/), which provides a 360-degree vision about 5G. As a companion initiative, CNIT also edited this book, with the aim of overviewing the status of 5G and of documenting the Italian involvement in 5G research and experimentation. This book will have a first version, printed and presented at the 5G Italy event, but then it will continue to live and grow on the web, updated with contributions coming from the conference. *CNIT (National, Inter-University Consortium for Telecommunications, https://www.cnit.it/) is a non-profit consortium, established in 1995, bringing together 37 public Italian universities to perform research, innovation and education/training activities in the field of Information and Communication Technology (ICT). More than 1,300 professors and researchers, belonging to the member universities, collaborate within CNIT, together with more than 100 CNIT own employees

Dynamic mobile base stations in 5G networks ::the moving network paradigm

The evolution of current wireless access networks towards 5G and beyond is characterized, among others, by the provisioning of high-bandwidth services and by the capability of serving traffic of a large number of heterogeneous devices. Among the key approaches for provisioning high capacity in such networks, a prominent role is played by network densification. However, dense deployments of many small cell base stations imply huge investments, increasing both CAPEX and OPEX for the mobile network. Additionally, densification increases the amount of overprovisioned network resources, due to variability in traffic demand over space and time. One of the most promising approaches to address these issues is the moving network paradigm, which exploits vehicle-mounted small cell moving base stations. This allows taking advantage of the correlation between spatio-temporal patterns of users and of vehicles, in order to create a network that flexibly and naturally densifies whenever and wherever needed by “following” users, hence reducing the need for dense deployments of static base stations. In this chapter, we review the main motivations and drivers for integrating moving base stations into future cellular access networks, and we outline the overall network architecture resulting from such integration. Furthermore, we characterize some of the main open research issues which stand in the way of the practical feasibility of the moving network paradigm. Among these are questions such as how to efficiently manage network resources in a dynamic fashion, accounting for the dynamics of service demand as well as of the moving network infrastructure; how to mitigate interference effects; how to implement mechanisms for reliable wireless mobile backhaul, for the interconnection of moving base stations to the core of the network; and how to efficiently provision Multi-access Edge Computing (MEC) services in the moving network paradigm