Evaluation of a Load Profiling Approach to Routing Guaranteed Bandwidth Flows

To support the diverse Quality of Service (QoS) requirements of real-time (e.g. audio/video) applications in integrated services networks, several routing algorithms that allow for the reservation of the needed bandwidth over a Virtual Circuit (VC) established on one of several candidate routes have been proposed. Traditionally, such routing is done using the least-loaded concept, and thus results in balancing the load across the set of candidate routes. In a recent study, we have established the inadequacy of this load balancing practice and proposed the use of load profiling as an alternative. Load profiling techniques allow the distribution of "available" bandwidth across a set of candidate routes to match the characteristics of incoming VC QoS requests. In this paper we thoroughly characterize the performance of VC routing using load profiling and contrast it to routing using load balancing and load packing. We do so both analytically and via extensive simulations of multi-class traffic routing in Virtual Path (VP) based networks. Our findings confirm that for routing guaranteed bandwidth flows in VP networks, load balancing is not desirable as it results in VP bandwidth fragmentation, which adversely affects the likelihood of accepting new VC requests. This fragmentation is more pronounced when the granularity of VC requests is large. Typically, this occurs when a common VC is established to carry the aggregate traffic flow of many high-bandwidth real-time sources. For VP-based networks, our simulation results show that our load-profiling VC routing scheme performs better or as well as the traditional load-balancing VC routing in terms of revenue under both skewed and uniform workloads. Furthermore, load-profiling routing improves routing fairness by proactively increasing the chances of admitting high-bandwidth connections.

Effects of priming duration on retention over the first 1 1/2 years of life.

Exposing individuals to an isolated component (a prime) of a prior event alleviates its forgetting. Two experiments with 120 human infants between 3 and 18 months of age determined the minimum duration of a prime that can reactivate a forgotten memory and how long the reactivated memory persists. Infants learned an operant task, forgot it, were exposed to the prime, and later were tested for renewed retention. In Experiment 1, the minimum duration of an effective prime decreased logarithmically with age, but was always longer than the duration of a mere glance. In Experiment 2, the reactivated memory was forgotten twice as fast after a minimum-duration prime as after a full-length one, irrespective of priming delay and infant age. These data reveal that the minimum effective prime duration psychophysically equates the accessibility of forgotten memories. We conclude that priming is perceptually based with effects that are organized on a ratio (log) scale.

Mechanisms of CD8+ T Cell Mediated Virus Inhibition in HIV-1 Virus Controllers

CD8+ T cells are associated with long term control of virus replication to low or undetectable levels in a population of HIV+ therapy-naïve individuals known as virus controllers (VCs; <5000 RNA copies/ml and CD4+ lymphocyte counts >400 cells/µl). These subjects' ability to control viremia in the absence of therapy makes them the gold standard for the type of CD8+ T-cell response that should be induced with a vaccine. Studying the regulation of CD8+ T cells responses in these VCs provides the opportunity to discover mechanisms of durable control of HIV-1. Previous research has shown that the CD8+ T cell population in VCs is heterogeneous in its ability to inhibit virus replication and distinct T cells are responsible for virus inhibition. Further defining both the functional properties and regulation of the specific features of the select CD8+ T cells responsible for potent control of viremia the in VCs would enable better evaluation of T cell-directed vaccine strategies and may inform the design of new therapies.

Here we discuss the progress made in elucidating the features and regulation of CD8+ T cell response in virus controllers. We first detail the development of assays to quantify CD8+ T cells' ability to inhibit virus replication. This includes the use of a multi-clade HIV-1 panel which can subsequently be used as a tool for evaluation of T cell directed vaccines. We used these assays to evaluate the CD8+ response among cohorts of HIV-1 seronegative, HIV-1 acutely infected, and HIV-1 chronically infected (both VC and chronic viremic) patients. Contact and soluble CD8+ T cell virus inhibition assays (VIAs) are able to distinguish these patient groups based on the presence and magnitude of the responses. When employed in conjunction with peptide stimulation, the soluble assay reveals peptide stimulation induces CD8+ T cell responses with a prevalence of Gag p24 and Nef specificity among the virus controllers tested. Given this prevalence, we aimed to determine the gene expression profile of Gag p24-, Nef-, and unstimulated CD8+ T cells. RNA was isolated from CD8+ T-cells from two virus controllers with strong virus inhibition and one seronegative donor after a 5.5 hour stimulation period then analyzed using the Illumina Human BeadChip platform (Duke Center for Human Genome Variation). Analysis revealed that 565 (242 Nef and 323 Gag) genes were differentially expressed in CD8+ T-cells that were able to inhibit virus replication compared to those that could not. We compared the differentially expressed genes to published data sets from other CD8+ T-cell effector function experiments focusing our analysis on the most recurring genes with immunological, gene regulatory, apoptotic or unknown functions. The most commonly identified gene in these studies was TNFRSF9. Using PCR in a larger cohort of virus controllers we confirmed the up-regulation of TNFRSF9 in Gag p24 and Nef-specific CD8+ T cell mediated virus inhibition. We also observed increase in the mRNA encoding antiviral cytokines macrophage inflammatory proteins (MIP-1α, MIP-1αP, MIP-1β), interferon gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), and recently identified lymphotactin (XCL1).

Our previous work suggests the CD8+ T-cell response to HIV-1 can be regulated at the level of gene regulation. Because RNA abundance is modulated by transcription of new mRNAs and decay of new and existing RNA we aimed to evaluate the net rate of transcription and mRNA decay for the cytokines we identified as differentially regulated. To estimate rate of mRNA synthesis and decay, we stimulated isolated CD8+ T-cells with Gag p24 and Nef peptides adding 4-thiouridine (4SU) during the final hour of stimulation, allowing for separation of RNA made during the final hour of stimulation. Subsequent PCR of RNA isolated from these cells, allowed us to determine how much mRNA was made for our genes of interest during the final hour which we used to calculate rate of transcription. To assess if stimulation caused a change in RNA stability, we calculated the decay rates of these mRNA over time. In Gag p24 and Nef stimulated T cells , the abundance of the mRNA of many of the cytokines examined was dependent on changes in both transcription and mRNA decay with evidence for potential differences in the regulation of mRNA between Nef and Gag specific CD8+ T cells. The results were highly reproducible in that in one subject that was measured in three independent experiments the results were concordant.

This data suggests that mRNA stability, in addition to transcription, is key in regulating the direct anti-HIV-1 function of antigen-specific memory CD8+ T cells by enabling rapid recall of anti-HIV-1 effector functions, namely the production and increased stability of antiviral cytokines. We have started to uncover the mechanisms employed by CD8+ T cell subsets with antigen-specific anti-HIV-1 activity, in turn, enhancing our ability to inhibit virus replication by informing both cure strategies and HIV-1 vaccine designs that aim to reduce transmission and can aid in blocking HIV-1 acquisition.

Characterization of B cells in muscle-specific kinase antibody myasthenia gravis.

OBJECTIVE: To characterize B-cell subsets in patients with muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG). METHODS: In accordance with Human Immunology Project Consortium guidelines, we performed polychromatic flow cytometry and ELISA assays in peripheral blood samples from 18 patients with MuSK MG and 9 healthy controls. To complement a B-cell phenotype assay that evaluated maturational subsets, we measured B10 cell percentages, plasma B cell-activating factor (BAFF) levels, and MuSK antibody titers. Immunologic variables were compared with healthy controls and clinical outcome measures. RESULTS: As expected, patients treated with rituximab had high percentages of transitional B cells and plasmablasts and thus were excluded from subsequent analysis. The remaining patients with MuSK MG and controls had similar percentages of total B cells and naïve, memory, isotype-switched, plasmablast, and transitional B-cell subsets. However, patients with MuSK MG had higher BAFF levels and lower percentages of B10 cells. In addition, we observed an increase in MuSK antibody levels with more severe disease. CONCLUSIONS: We found prominent B-cell pathology in the distinct form of MG with MuSK autoantibodies. Increased BAFF levels have been described in other autoimmune diseases, including acetylcholine receptor antibody-positive MG. This finding suggests a role for BAFF in the survival of B cells in MuSK MG, which has important therapeutic implications. B10 cells, a recently described rare regulatory B-cell subset that potently blocks Th1 and Th17 responses, were reduced, which suggests a potential mechanism for the breakdown in immune tolerance in patients with MuSK MG.

Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis.

Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in CD39 expression or Treg number.

Similar prevalence and magnitude of auditory-evoked and visually evoked activity in the frontal eye fields: implications for multisensory motor control.

Saccadic eye movements can be elicited by more than one type of sensory stimulus. This implies substantial transformations of signals originating in different sense organs as they reach a common motor output pathway. In this study, we compared the prevalence and magnitude of auditory- and visually evoked activity in a structure implicated in oculomotor processing, the primate frontal eye fields (FEF). We recorded from 324 single neurons while 2 monkeys performed delayed saccades to visual or auditory targets. We found that 64% of FEF neurons were active on presentation of auditory targets and 87% were active during auditory-guided saccades, compared with 75 and 84% for visual targets and saccades. As saccade onset approached, the average level of population activity in the FEF became indistinguishable on visual and auditory trials. FEF activity was better correlated with the movement vector than with the target location for both modalities. In summary, the large proportion of auditory-responsive neurons in the FEF, the similarity between visual and auditory activity levels at the time of the saccade, and the strong correlation between the activity and the saccade vector suggest that auditory signals undergo tailoring to match roughly the strength of visual signals present in the FEF, facilitating accessing of a common motor output pathway.

Clinical utility of a Web-enabled risk-assessment and clinical decision support program.

PURPOSE: Risk-stratified guidelines can improve quality of care and cost-effectiveness, but their uptake in primary care has been limited. MeTree, a Web-based, patient-facing risk-assessment and clinical decision support tool, is designed to facilitate uptake of risk-stratified guidelines. METHODS: A hybrid implementation-effectiveness trial of three clinics (two intervention, one control). PARTICIPANTS: consentable nonadopted adults with upcoming appointments. PRIMARY OUTCOME: agreement between patient risk level and risk management for those meeting evidence-based criteria for increased-risk risk-management strategies (increased risk) and those who do not (average risk) before MeTree and after. MEASURES: chart abstraction was used to identify risk management related to colon, breast, and ovarian cancer, hereditary cancer, and thrombosis. RESULTS: Participants = 488, female = 284 (58.2%), white = 411 (85.7%), mean age = 58.7 (SD = 12.3). Agreement between risk management and risk level for all conditions for each participant, except for colon cancer, which was limited to those <50 years of age, was (i) 1.1% (N = 2/174) for the increased-risk group before MeTree and 16.1% (N = 28/174) after and (ii) 99.2% (N = 2,125/2,142) for the average-risk group before MeTree and 99.5% (N = 2,131/2,142) after. Of those receiving increased-risk risk-management strategies at baseline, 10.5% (N = 2/19) met criteria for increased risk. After MeTree, 80.7% (N = 46/57) met criteria. CONCLUSION: MeTree integration into primary care can improve uptake of risk-stratified guidelines and potentially reduce "overuse" and "underuse" of increased-risk services.Genet Med 18 10, 1020-1028.

Contribution to the knowlegde of Galician xenoflora (NW Iberian Peninsula, Spain).

Information on 12 exotic plants of diverse interest for the Galician flora are presented. All of them were collected in Ribeira council (SW of the A Coruña province). The total includes 8 novelties at a regional level (Aeonium haworthii, Aloe mitriformis, Brugmansia × candida, Nephrolepis cordifolia, Osteospermum ecklonis, Pelargonium capitatum, Sedum mexicanum, Sparaxis tricolor), and 2 provincial novelties. In addition, information on two taxa hardly mentioned in the literature on Galician vascular flora is also included. All the cited specimens are deposited at the SANT Herbarium.

Perspectives and Integration in SOLAS Science

Why a chapter on Perspectives and Integration in SOLAS Science in this book? SOLAS science by its nature deals with interactions that occur: across a wide spectrum of time and space scales, involve gases and particles, between the ocean and the atmosphere, across many disciplines including chemistry, biology, optics, physics, mathematics, computing, socio-economics and consequently interactions between many different scientists and across scientific generations. This chapter provides a guide through the remarkable diversity of cross-cutting approaches and tools in the gigantic puzzle of the SOLAS realm. Here we overview the existing prime components of atmospheric and oceanic observing systems, with the acquisition of ocean–atmosphere observables either from in situ or from satellites, the rich hierarchy of models to test our knowledge of Earth System functioning, and the tremendous efforts accomplished over the last decade within the COST Action 735 and SOLAS Integration project frameworks to understand, as best we can, the current physical and biogeochemical state of the atmosphere and ocean commons. A few SOLAS integrative studies illustrate the full meaning of interactions, paving the way for even tighter connections between thematic fields. Ultimately, SOLAS research will also develop with an enhanced consideration of societal demand while preserving fundamental research coherency.

Biomass changes and trophic amplification of plankton in a warmer ocean

Ocean warming can modify the ecophysiology and distribution of marine organisms, and relationships between species, with nonlinear interactions between ecosystem components potentially resulting in trophic amplification. Trophic amplification (or attenuation) describe the propagation of a hydroclimatic signal up the food web, causing magnification (or depression) of biomass values along one or more trophic pathways. We have employed 3-D coupled physical-biogeochemical models to explore ecosystem responses to climate change with a focus on trophic amplification. The response of phytoplankton and zooplankton to global climate-change projections, carried out with the IPSL Earth System Model by the end of the century, is analysed at global and regional basis, including European seas (NE Atlantic, Barents Sea, Baltic Sea, Black Sea, Bay of Biscay, Adriatic Sea, Aegean Sea) and the Eastern Boundary Upwelling System (Benguela). Results indicate that globally and in Atlantic Margin and North Sea, increased ocean stratification causes primary production and zooplankton biomass to decrease in response to a warming climate, whilst in the Barents, Baltic and Black Seas, primary production and zooplankton biomass increase. Projected warming characterized by an increase in sea surface temperature of 2.29 ± 0.05 °C leads to a reduction in zooplankton and phytoplankton biomasses of 11% and 6%, respectively. This suggests negative amplification of climate driven modifications of trophic level biomass through bottom-up control, leading to a reduced capacity of oceans to regulate climate through the biological carbon pump. Simulations suggest negative amplification is the dominant response across 47% of the ocean surface and prevails in the tropical oceans; whilst positive trophic amplification prevails in the Arctic and Antarctic oceans. Trophic attenuation is projected in temperate seas. Uncertainties in ocean plankton projections, associated to the use of single global and regional models, imply the need for caution when extending these considerations into higher trophic levels.

A comprehensive study of visual cryptography

In this survey, we will summarize the latest developments of visual cryptography since its inception in 1994, introduce the main research topics in this area and outline the current problems and possible solutions. Directions and trends for future VC work shall also be examined along with possible VC applications.

A quantitative research on S- and SO2-poisoning Pt/Vulcan carbon fuel cell catalyst

A quantitative research on S and SO2 poisoning Pt/Vulcan carbon (Pt/VC) catalysts for fuel cells was conducted by the three-electrode method. Pt/VC electrodes were contaminated by submersion in a SO2- containing solution made up of 0.2 mM Na2SO3 and 0.5 M H2SO4 for different periods of time, and held at 0.05 V (vs. RHE) in 0.5 M H2SO4 solutions in order to gain zero-valence sulfur (S0) poisoned electrodes. The sulfur coverage of Pt was determined from the total charge consumed as the sulfur was oxidized from S0 at 0.05 V (vs. RHE) to sulfate at >1.1 V (vs. RHE). The summation of initial coverage of S0 (S) and coverage of H (H) are approximately equal to 1 (H + S = 1) when 0.5

Exploring Virtual-Channel architecture in FPGA based Networks-on-Chip

A novel Networks-on-Chip (NoC) router architecture specified for FPGA based implementation with configurable Virtual-Channel (VC) is presented. Each pipeline stage of the proposed architecture has been optimized so that low packet propagation latency and reduced hardware overhead can be achieved. The proposed architecture enables high performance and cost effective VC NoC based on-chip system interconnects to be deployed on FPGA.

Ion-acoustic supersolitons in plasmas with two-temperature electrons: Boltzmann and kappa distributions

Acoustic supersolitons arise when a plasma model is able to support three consecutive local extrema of the Sagdeev pseudopotential between the undisturbed conditions and an accessible root. This leads to a characteristic electric field signature, where a simple bipolar shape is enriched by subsidiary maxima. Large-amplitude nonlinear acoustic modes are investigated, using a pseudopotential approach, for plasmas containing two-temperature electrons having Boltzmann or kappa distributions, in the presence of cold fluid ions. The existence domains for positive supersolitons are derived in a methodological way, both for structure velocities and amplitudes, in terms of plasma compositional parameters. In addition, typical pseudopotentials, soliton, and electric field profiles have been given to illustrate that positive supersolitons can be found in the whole range of electron distributions from Maxwellian to a very hard nonthermal spectrum in kappa. However, it is found that the parameter ranges that support supersolitons vary significantly over the wide range of kappa considered. VC 2013 AIP Publishing LLC. [http://dx.doi.org/10.1063/1.4818888]