Antibody-antigen interactions: What is the required time to equilibrium?

The use of antibodies is widespread in many areas including in-vivo and in-vitro diagnostics, quantitative analysis in research laboratories and as therapeutic substances. Since the methods for generation of antibodies has improved and regularly results in high-affinity interactions, the standard assays used for quantification of the interaction properties should be revisited because they do not necessarily produce accurate results. Here we show that in several cases, the affinity determination of strongly binding antibodies will be inherently difficult when using standard procedures, due to impractically long incubation times. Real-time kinetic analysis is often the only realistic alternative for affinity determination

Identification of Virulence Factors in Nematode-Trapping Fungi - Insights from Genomics, Transcriptomics and Proteomics

Nematode-trapping fungi are soil-living organisms with the unique ability to capture and infect free-living nematodes. The interest in studying these fungi arises from their potential use as biological control agents for plant- and animal-parasitic nematodes. To enter the parasitic stage, nematode-trapping fungi develop different kinds of trapping structures. In order to understand more about the evolution of parasitism in the nematode-trapping fungi and to identify virulence factors in these fungi genomic, transcriptomic and proteomic studies were conducted. First, the genome of Monacrosporium haptotylum was sequenced and compared to the genome of the closely related Arthrobotrys oligospora and also to genomes of other ascomycetes. Two genomic mechanisms were identified that likely have been important for the adaptation to parasitism in these two nematode-trapping fungi. Firstly, the expansion of certain protein-domain families and a large number of species-specific genes indicated that gene duplications followed by functional diversification have played a major role in the evolution of the nematode-trapping fungi. Gene expression analyses indicated that many of these genes are important for pathogenicity. Secondly, comparisons of gene expression of orthologs between the two fungi during infection indicated that differential regulation was an important mechanism for the evolution of parasitism in nematode-trapping fungi. Second, the proteome of the trapping structure in M. haptotylum was characterized using mass spectrometry. The trapping structure in this fungus is called knob and is a single cell that can be separated from the vegetative mycelia. The results showed that there was a large difference in the protein content of the knob and that of the mycelium. The knob proteome was overrepresented in secreted proteins, including small secreted proteins, peptidases and proteins containing the carbohydrate-binding domain WSC. Transcripts encoding such proteins were also highly upregulated in M. haptotylum during infection. We suggest that the knob contains many of the proteins needed in the early stages of infection. Finally, to gain further insight about what genes that are generally regulated during infection we conducted a comparative transcriptome analysis of three nematode-trapping fungi infecting two nematode species. The analysis showed that the divergence in fungal interspecific gene expression was significantly larger than that related to the nematode host. We identified a core set of genes being expressed by all three fungi, and a more variable set being regulated depending on the fungal species or nematode host, respectively. The core set included several peptidases such as subtilisins and aspartic proteases but also ribosome-inactivating Ricin-B lectins. The variable set depending on the fungal species included fungal fruit-body lectins and D-mannose binding lectins. The host specific genes included glucosidases and genes encoding small secreted proteins

Distributed Primary Frequency Control through Multi-Terminal HVDC Transmission Systems

This paper presents a decentralized controller for sharing primary AC frequency control reserves through a multi-terminal HVDC grid. By using Lyapunov arguments, the proposed controller is shown to stabilize the equilibrium of the closed-loop system consisting of the interconnected AC and HVDC grids, given any positive controller gains. The static control errors resulting from the proportional controller are quantified and bounded by analyzing the equilibrium of the closed-loop system. The proposed controller is applied to a test grid consisting of three asynchronous AC areas interconnected by an HVDC grid, and its effectiveness is validated through simulation

Distributed Secondary Frequency Control through MTDC Transmission Systems

In this paper, we present distributed controllers for sharing primary and secondary frequency control reserves for asynchronous AC transmission systems, which are connected through a multi-terminal HVDC grid. By using Lyapunov arguments, the equilibria of the closed-loop system are shown to be globally asymptotically stable. We quantify the static errors of the voltages and frequencies, and give upper bounds for these errors. It is also shown that the controllers have the property of power sharing, i.e., primary and secondary frequency control reserves are shared fairly amongst the AC systems. The proposed controllers are applied to a high-order dynamic model of of a power system consisting of asynchronous AC grids connected through a six-terminal HVDC grid.Comment: arXiv admin note: text overlap with arXiv:1409.801

Predictability modulates the affective and sensory-discriminative neural processing of pain

Knowing what is going to happen next, that is, the capacity to predict upcoming events, modulates the extent to which aversive stimuli induce stress and anxiety. We explored this issue by manipulating the temporal predictability of aversive events by means of a visual cue, which was either correlated or uncorrelated with pain stimuli (electric shocks). Subjects reported lower levels of anxiety, negative valence and pain intensity when shocks were predictable. In addition to attenuate focus on danger, predictability allows for correct temporal estimation of, and selective attention to, the sensory input. With functional magnetic resonance imaging, we found that predictability was related to enhanced activity in relevant sensory-discriminative processing areas, such as the primary and secondary sensory cortex and posterior insula. In contrast, the unpredictable more aversive context was correlated to brain activity in the anterior insula and the orbitofrontal cortex, areas associated with affective pain processing. This context also prompted increased activity in the posterior parietal cortex and lateral prefrontal cortex that we attribute to enhanced alertness and sustained attention during unpredictability. (c) 2006 Elsevier Inc. All rights reserved.This study was supported by grants from The Swedish Research Council (2003-5810), The family Hedlund Foundation and Karolinska Institutet. The project was finished in the context of Stockholm Brain Institute.info:eu-repo/semantics/publishedVersio

Security and Privacy for Smart, Connected, and Mobile IoT Devices and Platforms

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Could flies explain the elusive epidemiology of campylobacteriosis?

BACKGROUND: Unlike salmonellosis with well-known routes of transmission, the epidemiology of campylobacteriosis is still largely unclear. Known risk factors such as ingestion of contaminated food and water, direct contact with infected animals and outdoor swimming could at most only explain half the recorded cases. DISCUSSION: We put forward the hypothesis that flies play a more important role in the transmission of the bacteria, than has previously been recognized. Factors supporting this hypothesis are: 1) the low infective dose of Campylobacter; 2) the ability of flies to function as mechanical vectors; 3) a ubiquitous presence of the bacteria in the environment; 4) a seasonality of the disease with summer peaks in temperate regions and a more evenly distribution over the year in the tropics; 5) an age pattern for campylobacteriosis in western travellers to the tropics suggesting other routes of transmission than food or water; and finally 6) very few family clusters. SUMMARY: All the evidence in favour of the fly hypothesis is circumstantial and there may be alternative explanations to each of the findings supporting the hypothesis. However, in the absence of alternative explanations that could give better clues to the evasive epidemiology of Campylobacter infection, we believe it would be unwise to rule out flies as important mechanical vectors also of this disease