This policy paper aims to contribute to understanding the recent debate on fair cost sharing between Big Techs and European telecommunication operators who offer complementary services: content and ...access to the Internet. We take stock from recent economic literature and empirical evidences to show the differences in business models and regulatory constraints have led to unequal net benefits from growing European digital economy. In particular, because the telecommunication operators have to bear the costs of delivering content to end-users, their business can be strongly affected due to the sharp increase in traffic generation. This negative externality should be internalized to correct the related market failure and to restore incentives to invest in the network infrastructure to meet the ambitious Europe's Digital Decade targets. Furthermore, we assess the interplay between access and content, and demonstrate how a fair cost sharing policy can impact investment, consumer surplus and social welfare. In particular, content providers that are efficient in monetizing consumers are incentivized to lower the cost of content to consumers, which positively impacts the consumer surplus and social welfare. Also, because cost sharing can even encourage digital platforms to better optimize the demand, this could have potentially positive effect on the environment. Finally, we give some recommendations to effectively implement the policy in practice.
•Today, more than half of the network traffic comes from very few content providers.•The network costs are largely borne by network operators, and not content providers.•This highlights a negative externality problem due to the complementarity between the network and the content.•If the traffic is excessively generated, cost sharing can encourage investments and benefit consumers.•A regulatory negotiation framework could be an effective solution, and transparency is a major issue to watch out for.
Internet of Things (IoTs) has been playing an important role in many sectors, such as smart cities, smart agriculture, smart healthcare, and smart manufacturing. However, IoT devices are highly ...vulnerable to cyber-attacks, which may result in security breaches and data leakages. To effectively prevent these attacks, a variety of machine learning-based network intrusion detection methods for IoT networks have been developed, which often rely on either feature extraction or feature selection techniques for reducing the dimension of input data before being fed into machine learning models. This aims to make the detection complexity low enough for real-time operations, which is particularly vital in any intrusion detection systems. This paper provides a comprehensive comparison between these two feature reduction methods of intrusion detection in terms of various performance metrics, namely, precision rate, recall rate, detection accuracy, as well as runtime complexity, in the presence of the modern UNSW-NB15 dataset as well as both binary and multiclass classification. For example, in general, the feature selection method not only provides better detection performance but also lower training and inference time compared to its feature extraction counterpart, especially when the number of reduced features
K
increases. However, the feature extraction method is much more reliable than its selection counterpart, particularly when
K
is very small, such as
K
=
4
. Additionally, feature extraction is less sensitive to changing the number of reduced features
K
than feature selection, and this holds true for both binary and multiclass classifications. Based on this comparison, we provide a useful guideline for selecting a suitable intrusion detection type for each specific scenario, as detailed in Table
14
at the end of Sect.
4
. Note that such the comparison between feature selection and feature extraction over UNSW-NB15 as well as theoretical guideline have been overlooked in the literature.
Objective:To characterize viral co-infections among representative hospitalized measles cases during the 2014 Hanoi outbreak.Methods:Throat swabs were collected from 54 pediatric patients with ...confirmed measles,and molecular diagnostics performed for 10 additional viral respiratory pathogens(Influenza A/H1N1pdm09;A/H3N2 and influenza B;Parainfluenza 1,2,3;Respiratory Synctial Virus,RSV;human Metapneumovirus,hM PV;Adenovirus and Picornavirus).Results:Twenty-one cases(38.9%) showed evidence of infection with other respiratory viruses:15 samples contained measles plus one additional virus,and 6 samples contained measles plus 2 additional viruses.Adenovirus was detected as a predominant cause of co-infections(13 cases;24.1%),followed by RSV(6 cases;11.1%),A/H1N1pdm09(3 cases;5.6%),PIV3(3 cases;3.7%),Rhinovirus(3 cases;3.7%) and hM PV(1 case;1.96%).Conclusions:Viral co-infections identified from pediatric measles cases may have contributed to increased disease severity and high rate of fatal outcomes.Optimal treatment of measles cases may require control of multiple viral respiratory pathogens.
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health concern. The development of vaccines with high ...immunogenicity and safety is crucial for controlling the global COVID-19 pandemic and preventing further illness and fatalities. Here, we report the development of a SARS-CoV-2 vaccine candidate, Nanocovax, based on recombinant protein production of the extracellular (soluble) portion of the spike (S) protein of SARS-CoV-2. The results showed that Nanocovax induced high levels of S protein-specific IgG and neutralizing antibodies in three animal models: BALB/c mouse, Syrian hamster, and a non-human primate (
). In addition, a viral challenge study using the hamster model showed that Nanocovax protected the upper respiratory tract from SARS-CoV-2 infection. Nanocovax did not induce any adverse effects in mice (
var. albino) and rats (
). These preclinical results indicate that Nanocovax is safe and effective.
Summary
Phenol‐soluble modulin (PSM) is a peptide complex produced by the nosocomial pathogen Staphylococcus epidermidis that has a strong capacity to activate the human innate immune response. We ...developed a novel method based on liquid chromatography‐mass spectrometry (LC‐MS) to quantify the production of the individual PSM components. Each PSM peptide was abundant in most of the 76 S epidermidis strains tested. Importantly, none of the PSM components were secreted by an agr mutant strain, indicating that PSM synthesis is regulated strictly by the agr quorum‐sensing system. Furthermore, the agr mutant strain failed to elicit production of TNFα by human myeloid cells and induced significantly less neutrophil chemotaxis compared with the wild‐type strain. Thus, quorum‐sensing in S. epidermidis dramatically influenced activation of human host defence. We propose that an agr quorum‐sensing mechanism facilitates growth and survival in infected hosts by adapting production of the pro‐inflammatory PSMs to the stage of infection.
The role of the influenza virus polymerase complex in host range restriction has been well-studied and several host range determinants, such as the polymerase PB2-E627K and PB2-D701N mutations, have ...been identified. However, there may be additional, currently unknown, human adaptation polymerase mutations. Here, we used a database search of influenza virus H5N1 clade 1.1, clade 2.3.2.1 and clade 2.3.4 strains isolated from 2008-2012 in Southern China, Vietnam and Cambodia to identify polymerase adaptation mutations that had been selected in infected patients. Several of these mutations acted either alone or together to increase viral polymerase activity in human airway cells to levels similar to the PB2-D701N and PB2-E627K single mutations and to increase progeny virus yields in infected mouse lungs to levels similar to the PB2-D701N single mutation. In particular, specific mutations acted synergistically with the PB2-D701N mutation and showed synergistic effects on viral replication both in human airway cells and mice compared with the corresponding single mutations. Thus, H5N1 viruses in infected patients were able to acquire multiple polymerase mutations that acted cooperatively for human adaptation. Our findings give new insight into the human adaptation of AI viruses and help in avian influenza virus risk assessment.
Staphylococci are important opportunistic pathogens. However, there is a lack of information on how these bacteria survive inside the human body during infection. This study demonstrates that ...quorum-sensing regulation in Staphylococcus epidermidis protects it from key mechanisms of human innate host defense. To gain a better understanding of the basis of the observed phenotype, the agr quorum-sensing regulon of S. epidermidis was characterized by a genomewide analysis of gene expression. The gene-expression data indicate that agr adapts bacterial physiology to stationary growth and, furthermore, that it controls a series of virulence factors, including degradative exoenzymes possibly involved in resistance to antimicrobial peptides. Remarkably, agr also regulates general and oxidative stress-response factors, including detoxifying enzymes of reactive oxygen species. Taken together, the results of this study indicate that quorum-sensing regulation in staphylococci has important, previously unknown functions that contribute to protection from mechanisms of human innate host defense—and, therefore, to the pathogen’s survival in the human host
The physiological significance of the accessory gene regulator (agr) system of Staphylococcus epidermidis was investigated by construction of an agr deletion mutant via allelic replacement with a ...spectinomycin resistance cassette. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that the protein pattern was strongly altered in the mutant; the amounts of most surface proteins were higher, whereas the amounts of most exoproteins were lower. The agr system of S. epidermidis thus appears to have an important impact on growth phase-dependent protein synthesis as has been shown for Staphylococcus aureus. The activity of the exoenzymes lipase and protease, assumed to be involved in staphylococcal pathogenicity, was investigated by agar diffusion assays and SDS-PAGE activity staining. A general reduction of these enzyme activities in the agr mutant was found. The difference in overall lipase activity was small, but zymographic analysis suggested a clear defect in lipase processing in the agr mutant.
Mutation and reassortment of highly pathogenic avian influenza A(H5N1) viruses at the animal–human interface remain a major concern for emergence of viruses with pandemic potential. To understand the ...relationship of H5N1 viruses circulating in poultry and those isolated from humans, comprehensive phylogenetic and molecular analyses of viruses collected from both hosts in Vietnam between 2003 and 2010 were performed. We examined the temporal and spatial distribution of human cases relative to H5N1 poultry outbreaks and characterized the genetic lineages and amino acid substitutions in each gene segment identified in humans relative to closely related viruses from avian hosts. Six hemagglutinin clades and 8 genotypes were identified in humans, all of which were initially identified in poultry. Several amino acid mutations throughout the genomes of viruses isolated from humans were identified, indicating the potential for poultry viruses infecting humans to rapidly acquire molecular markers associated with mammalian adaptation and antiviral resistance.