Engineering a QoS Provider Mechanism for Edge Computing with Deep Reinforcement Learning

With the development of new system solutions that integrate traditional cloud computing with the edge/fog computing paradigm, dynamic optimization of service execution has become a challenge due to the edge computing resources being more distributed and dynamic. How to optimize the execution to provide Quality of Service (QoS) in edge computing depends on both the system architecture and the resource allocation algorithms in place. We design and develop a QoS provider mechanism, as an integral component of a fog-to-cloud system, to work in dynamic scenarios by using deep reinforcement learning. We choose reinforcement learning since it is particularly well suited for solving problems in dynamic and adaptive environments where the decision process needs to be frequently updated. We specifically use a Deep Q-learning algorithm that optimizes QoS by identifying and blocking devices that potentially cause service disruption due to dynamicity. We compare the reinforcement learning based solution with state-of-the-art heuristics that use telemetry data, and analyze pros and cons

Charakterisierung des Core-Proteins von Pestiviren

Die subzelluläre Lokalisierung und die RNS bindende Aktivität des Core-Proteins von Pestiviren wurden untersucht und folgende Ergebnisse erzielt: 1.- Das Gen des Core-Proteins von KSPV und BVDV wurde in einen prokaryotischen Expressionsvektor kloniert, das Core-Protein in Bakterien (E. coli) exprimiert und durch „Immobilized Metal Affinity Chromatography“ (IMAC) in hohem Maß gereinigt. Dieses Protein fand Anwendung als Antigen zur Herstellung von mAks und stellte die Basis eines RNS-Bindungsassays dar. 2.- Ein System zum Screening von Hybridom Überständen wurde entwickelt, mit dem acht anti Core-Protein mAk produzierende Hybridome isoliert wurden. Die Anwendung der hergestellten mAks ermöglichte die Detektion des Core-Proteins von 13 Pestiviren verschiedener Spezies [BVDV-1 (7 Stämme); BVDV-2 (2 Stämme); BDV (2 Stämme); KSPV; Giraffe] in infizierten Zellen und aufkonzentrierten Virionen. 3.- Ein Disulfid verbrücktes Core-Protein Homodimer wurde in Virionen von BVDV-2 Stämmen identifiziert und mittels reverser Genetik charakterisiert. Wie bei den Flaviviren kommt das Core-Protein in Virionen von Pestiviren sehr wahrscheinlich als Dimer vor. 4.- In infizierten Zellen kolokalisierte das Core-Protein mit dem endoplasmatischen Retikulum und mit den Mitochondrien. Auch wurde dieses Protein in Assoziation mit den „RNA-processing bodies“ („P-Bodies“) nachgewiesen, welche eine wichtige Rolle bei der Regulation der Translation spielen. Eine Kolokalisierung des Core-Proteins mit Komponenten der pestiviralen Replikase, nämlich NS3 und NS5B, wurde festgestellt. Das NS5B (virale RNS-abhängige RNS-Polymerase) wurde, wie die drei Strukturproteine Erns, E1 und E2, überwiegend ER assoziiert nachgewiesen. Aufgrund seiner Verteilung könnte das Core-Protein in der infizierten Zelle Prozesse wie z.B. Translation beeinflussen. Die Lokalisierung der Nichtstruktur- bzw. Strukturproteine deutet darauf hin, dass „assembly“ und Replikation bei Pestiviren in demselben Kompartiment stattfinden. 5.- Ein Agarose RNS-Bindungsassay wurde zur Untersuchung der RNS-Bindungsaktivität des Core-Proteins entwickelt. Das Core-Protein band RNS sequenzunabhängig und somit kann die Inkorporation genomischer RNS in die pestiviralen Virionen aufgrund einer spezifischen RNS bindenden Aktivität des Core-Proteins ausgeschlossen werden. Sehr wahrscheinlich wird es durch das zeitlich koordinierte Erfolgen der Replikation des viralen Genoms und des Virus „assembly“ ermöglicht.The subcellular localization and RNA binding activity of the core-protein from pestiviruses were studied and the following results were obtained: 1.- The gene of the core-protein from CSFV and BVDV was cloned in a prokaryotic expression vector. After expression in bacteria (E. coli) the protein was purified by „Immobilized Methal Affinity Chromatography“ (IMAC), and used as antigen to produce mAbs and also in a RNA-binding assay. 2.- A system for the screening from hybridoma supernatants was developed which allowed the isolation of eight hybridomas that produce an core-protein mAbs. The generated mAbs proved to be useful to detect the core-protein of different Pestivirus species [BVDV-1 (7 strains); BVDV-2 (2 strains); BDV (2 strains); CSFV; giraffe] in infected cells and concentrated virions. 3.- A core-protein disulfide bond-linked homodimer was identified in virions from BVDV-2 strains and was characterized by reverse genetics. It is very probable that, like the core-protein from flaviviruses, the pestiviral core-protein is found as a dimer in virions. 4.- In infected cells the core-protein colocalized with the endoplasmic reticulum und mitochondria. This protein was also found in association with „RNA-processing bodies“ („P-Bodies“), which play an important role in the regulation of translation. The core-protein also colocalized with components of the pestiviral replicase, namely NS3 and NS5B. The NS5B (viral RNA-dependent RNA polymerase), and the three structural proteins Erns, E1 und E2 associated mainly with the endoplasmic reticulum. Due to its distribution in the infected cell the core-protein could influence processes like i.e. translation. The localization patterns of the nonstructural and structural proteins indicate that in the case of pestiviruses assembly and replication could take place in the same compartment. 5.- An agarose RNA-binding assay was developed to study the RNA-binding activity of the core-protein. The core-protein bound RNA in a sequence independent manner, which excludes the possibility that the incorporation of viral genomes in the virions is due to a sequence specific interaction of the core-protein with the pestiviral RNA. Instead the specific incorporation of the viral genome very likely occurs due to the compartimentalized and time coordinated replication of the viral genome and the virus assembly

Vandetanib (ZD6474) in the Treatment of Medullary Thyroid Cancer

Vandetanib (ZD6474) is an orally bioavailable small molecule tyrosine kinase inhibitor of multiple growth factor receptors, including RET (Rearrange during transfection), vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR). The activity against RET and VEGF made it a good choice in the treatment of medullary thyroid cancer (MTC). As there is considerable cross talk between growth factor pathways, dual inhibition with such agents has become an attractive strategy, in the treatment of many malignancies with encouraging Phase II clinical trial data to date. Vandetanib was tested in two Phase II trials in the treatment of patients with medullary thyroid cancer at doses of 100 mg and 300 mg daily respectively. The encouraging results of these 2 trials led to a randomized phase II trial comparing this medication to placebo using a crossover design. More than 300 patients were included in this study, which ultimately showed a significant improvement in progression-free survival in patients taking vandetanib. Based on these results, the Oncology Drug Advisory Committee (ODAC) of the Food and Drug Administration (FDA) recommended that vandetanib be approved for the treatment of patients with unresectable locally advanced or metastatic medullary thyroid cancer

Recovering actives in multi-antitarget and target design of analogs of the myosin II inhibitor blebbistatin

In multitarget drug design, it is critical to identify active and inactive compounds against a variety of targets and antitargets. Multitarget strategies thus test the limits of available technology, be that in screening large databases of compounds vs a large number of targets, or in using in silica methods for understanding and reliably predicting these pharmacological outcomes In this paper, we have evaluated the potential of several in silica approaches to predict the target, antitarget and physicochemical profile of (S)-blebbistatin, the best-known myosin II ATPase inhibitor, and a series of analogs thereof Standard and augmented structure-based design techniques could not recover the observed activity profiles A ligand-based method using molecular fingerprints was, however, able to select actives for myosin II inhibition Using further ligand- and structure-based methods, we also evaluated toxicity through androgen receptor binding, affinity for an array of antitargets and the ADME profile (including assay-interfering compounds) of the series In conclusion, in the search for (S)-blebbistatin analogs, the dissimilarity distance of molecular fingerprints to known actives and the computed antitarget and physicochemical profile of the molecules can be used for compound design for molecules with potential as tools for modulating myosin II and motility-related diseases

EFFECT OF Cr AND Pb ON THE ACTIVITY OF ANTIOXIDANT ENZYMES IN A CELL SUSPENSION CULTURE OF Jatropha curcas

Jatropha curcas is a tolerant and accumulator plant of heavy metals (HMs). Little is known about the mechanisms behind this ability. It is suggested that antioxidant enzymes might participate; however, there are no studies reporting the relationship between the activities of antioxidant enzymes and the presence of HMs in an in vitro cell suspension culture of J. curcas. The aim of this study was to determine the effect of chromium (Cr) or lead (Pb) at 0.0 to 3.0 mM on the activity of three antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX) through the growthofcellsuspensioncultures(CSC)ofJ.curcas. Theactivitydisplayedbythoseenzymeswasstatisticallysignificant (P≤0.05) when Cr or Pb was used. The greatest enzymatic activity was noted at the first hour of culture for SOD and at five h for POX and CAT. After 192 h, the activity of these three enzymes decreased, which coincided with the exponential growth phase of the cell culture. The results indicated that there is a close relationship between the presence of Cr and Pb and SOD, CAT, and POX activities in a cell suspension culture of J. curcas, which can explain the plant’s capability for tolerating and accumulating high concentrations of Cr and P

Bioaccessibility assay, antioxidant activity and consumer-oriented sensory analysis of Beta vulgaris by-product encapsulated in Ca(II)-alginate beads for different foods

Bioaccessibility analysis and antioxidant activity along in vitro digestion and a consumer-oriented sensory analysis were conducted in three potential functional foods based on Ca(II)-alginate beads containing bioactive compounds extracted from beet stems. Ca(II)-alginate beads per se, and two selected products (cookies and turkish delights supplemented with the beads) were prepared. Regarding the beads, among the attributes rated by consumers, visual appreciation predominates, being color in the just-as-right (JAR) category and in the like preference. Instead, both flavor and sweet taste were attributes highly penalized and should be improved in beads to be accepted as food per se. A higher percentage of customers preferred cookies and turkish delights instead of only beads, considering global satisfaction. Regarding in vitro digestion, there was a significant content of phenolic compounds in the products with beads, showing a bioaccessibility greater than 80% (for cookies) and 26% (for turkish delights). Also, the antioxidant capacity measured by ABTS ranged between 50 and 109% for cookies and turkish delights, being lower when measured by FRAP (between 20 and 30%, respectively). Thus, including the beads with beet stem extract in both products leads to a significant increase in the content of phenolic compounds and in the antioxidant capacity compared to their counterparts, protecting the compound during oral and gastric phases. These results allow the generation of improved Ca(II)-alginate systems with promising functional properties for the development of ingredients and functional foods.Fil: Aguirre Calvo, Tatiana Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; ArgentinaFil: Sosa, Natalia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Santa Fe. Instituto de Ciencia y Tecnologia de Los Alimentos de Entre Rios. - Universidad Nacional de Entre Rios. Instituto de Ciencia y Tecnologia de Los Alimentos de Entre Rios.; Argentina. Universidad Nacional de Entre Ríos. Facultad de Bromatología; ArgentinaFil: López, Tamara Anahí. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Santa Fe. Instituto de Ciencia y Tecnologia de Los Alimentos de Entre Rios. - Universidad Nacional de Entre Rios. Instituto de Ciencia y Tecnologia de Los Alimentos de Entre Rios.; Argentina. Universidad Nacional de Entre Ríos. Facultad de Bromatología; ArgentinaFil: Quintanilla Carvajal, María Ximena. Universidad de la Sabana; ColombiaFil: Perullini, Ana Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Santagapita, Patricio Roman. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentin

Isolation and characterization of new Puumala orthohantavirus strains from Germany

Orthohantaviruses are re-emerging rodent-borne pathogens distributed all over the world. Here, we report the isolation of a Puumala orthohantavirus (PUUV) strain from bank voles caught in a highly endemic region around the city Osnabrück, north-west Germany. Coding and non-coding sequences of all three segments (S, M, and L) were determined from original lung tissue, after isolation and after additional passaging in VeroE6 cells and a bank vole-derived kidney cell line. Different single amino acid substitutions were observed in the RNA-dependent RNA polymerase (RdRP) of the two stable PUUV isolates. The PUUV strain from VeroE6 cells showed a lower titer when propagated on bank vole cells compared to VeroE6 cells. Additionally, glycoprotein precursor (GPC)-derived virus-like particles of a German PUUV sequence allowed the generation of monoclonal antibodies that allowed the reliable detection of the isolated PUUV strain in the immunofluorescence assay. In conclusion, this is the first isolation of a PUUV strain from Central Europe and the generation of glycoprotein-specific monoclonal antibodies for this PUUV isolate. The obtained virus isolate and GPC-specific antibodies are instrumental tools for future reservoir host studies

Food Leftover Practices among Consumers in Selected Countries in Europe, South and North America

Foodborne illnesses may be related to many food production factors with home practices of consumers playing an important role in food safety. Consumer behavior for handling food leftovers has been studied, however little work on comparisons among countries has been published. The objective of this study was to investigate home food leftover practices of people from North American, South American, and European countries. Surveys were conducted with approximately 100 or more consumers in Argentina, Colombia, the United States, Estonia, Italy, Russia, and Spain. The participants responded to questions related to the length of time different types of food leftovers; such as meat, fresh salads, or restaurant dishes would be kept refrigerated or would be left at room temperature before refrigeration. Researchers also investigated how consumers would determine if the food was still safe for consumption. Potentially risky behaviors were observed in all seven countries. For instance, 55.8% of Estonians, 25% of Russians and 25.8% of Argentinean participants left food out at room temperature for several hours before storing in the refrigerator. Furthermore, 25%–29% of Colombian, Estonian, and Spanish consumers would look, smell, and taste leftovers to determine its probable safety. Correct handling of leftovers is an important aspect of consumer food safety. Although the surveys cannot be representative of all consumers in each country, they do provide an initial overview of comparative practices for handling leftovers among different countries. This provides government and educators with information on potential universal and unique consumer food safety issues related to handling leftover foods among various countries

Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus

New World arenaviruses are rodent-transmitted viruses and include a number of pathogens that are responsible for causing severe human disease. This includes Junín virus (JUNV), which is the causative agent of Argentine hemorrhagic fever. The wild nature and mobility of the rodent reservoir host makes it difficult to control the disease, and currently passive immunization with high-titer neutralizing antibody-containing plasma from convalescent patients is the only specific therapy. However, dwindling supplies of naturally available convalescent plasma, and challenges in developing similar resources for other closely related viruses, have made the development of alternative antibody-based therapeutic approaches of critical importance. In this study, we sought to induce a neutralizing antibody response in rabbits against the receptor-binding subunit of the viral glycoprotein, GP1, and the specific peptide sequences in GP1 involved in cellular receptor contacts. While these specific receptor-interacting peptides did not efficiently induce the production of neutralizing antibodies when delivered as a particulate antigen (as part of hepatitis B virus core-like particles), we showed that recombinant JUNV GP1 purified from transfected mammalian cells induced virus-neutralizing antibodies at high titers in rabbits. Further, neutralization was observed across a range of unrelated JUNV strains, a feature that is critical for effectiveness in the field. These results underscore the potential of GP1 alone to induce a potent neutralizing antibody response and highlight the importance of epitope presentation. In addition, effective virus neutralization by rabbit antibodies supports the potential applicability of this species for the future development of immunotherapeutics (e.g., based on humanized monoclonal antibodies). Such information can be applied in the design of vaccines and immunogens for both prevention and specific therapies against this and likely also other closely related pathogenic New World arenaviruses.Fil: Roman Sosa, Gleyder. Ulm University Hospital; AlemaniaFil: Leske, Anne. Friedrich-Loeffler-Institut; AlemaniaFil: Ficht, Xenia. Ulm University Hospital; AlemaniaFil: Dau, Tung Huy. Friedrich-Loeffler-Institut; AlemaniaFil: Holzerland, Julia. Friedrich-Loeffler-Institut; AlemaniaFil: Hoenen, Thomas. Friedrich-Loeffler-Institut; AlemaniaFil: Beer, Martin. Friedrich-Loeffler-Institut; AlemaniaFil: Kammerer, Robert. Friedrich-Loeffler-Institut; AlemaniaFil: Schirmbeck, Reinhold. Friedrich-Loeffler-Institut; AlemaniaFil: Rey, Felix A.. Friedrich-Loeffler-Institut; AlemaniaFil: Cordo, Sandra Myriam. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Groseth, Allison. Friedrich-Loeffler-Institut; Alemani

A Mechanistic Paradigm for Broad-Spectrum Antivirals that Target Virus-Cell Fusion

10.1371/journal.ppat.1003297PLoS Pathogens94