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Host-directed kinase inhibitors act as novel therapies against intracellular Staphylococcus aureus
Get PDFHost-directed therapeutics are a promising anti-infective strategy against intracellular bacterial pathogens. Repurposing host-targeted drugs approved by the FDA in the US, the MHRA in the UK and/or regulatory equivalents in other countries, is particularly interesting because these drugs are commercially available, safe doses are documented and they have been already approved for other clinical purposes. In this study, we aimed to identify novel therapies against intracellular Staphylococcus aureus, an opportunistic pathogen that is able to exploit host molecular and metabolic pathways to support its own intracellular survival. We screened 133 host-targeting drugs and found three host-directed tyrosine kinase inhibitors (Ibrutinib, Dasatinib and Crizotinib) that substantially impaired intracellular bacterial survival. We found that Ibrutinib significantly increased host cell viability after S. aureus infection via inhibition of cell invasion and intracellular bacterial proliferation. Using phosphoproteomics data, we propose a putative mechanism of action of Ibrutinib involving several host factors, including EPHA2, C-JUN and NWASP. We confirmed the importance of EPHA2 for staphylococcal infection in an EPHA2-knock-out cell line. Our study serves as an important example of feasibility for identifying host-directed therapeutics as candidates for repurposing
Identification of novel targets for host-directed therapeutics against intracellular Staphylococcus aureus
No full textDuring patient colonization, Staphylococcus aureus is able to invade and proliferate within human cells to evade the immune system and last resort drugs such as vancomycin. Hijacking specific host molecular factors and/or pathways is necessary for pathogens to successfully establish an intracellular infection. In this study, we employed an unbiased shRNA screening coupled with ultra-fast sequencing to screen 16,000 human genes during S. aureus infection and we identified several host genes important for this intracellular pathogen. In addition, we interrogated our screening results to find novel host-targeted therapeutics against intracellular S. aureus. We found that silencing the human gene TRAM2 resulted in a significant reduction of intracellular bacterial load while host cell viability was restored, showing its importance during intracellular infection. Furthermore, TRAM2 is an interactive partner of the endoplasmic reticulum SERCA pumps and treatment with the SERCA-inhibitor Thapsigargin halted intracellular MRSA survival. Our results suggest that Thapsigargin could be repurposed to tackle S. aureus host cell infection in combination with conventional antibiotics
Buffer-aided successive relay selection scheme for energy harvesting IoT networks
Get PDFIn this paper, we analyze the impact of buffer-aided full-duplex successive relay selection schemes with energy harvesting capability of relay nodes in amplifying and forward (AF) and decode and forward (DF) relaying environments for the Internet of Things networks. We propose to select a relay pair based on the energy harvested and signal strength at relay and destination to receive and transmit in the same time slot, respectively. Contrary to the previous relay pair selection schemes which are based on the signal strength only and cause the relay overuse problem, the proposed scheme ensures the balanced use of energy of relay nodes. The proposed relay selection scheme is implemented with the time switching (TS) and power splitting (PS)-based energy harvesting models in AF and DF relaying environments separately. Furthermore, we derive the closed-form expression of the outage probability and average throughput for both the TS and PS approaches in the DF and AF relaying modes. We compare the proposed relay selection scheme with the S-MMRS scheme and prove that the proposed scheme significantly reduces the outage probability and improves the average throughput. Furthermore, the analytical findings are reinforced with the extensive Monte Carlo simulations
Recent advances in tree root mapping and assessment using non-destructive testing methods: a focus on ground penetrating radar
Get PDFThis paper provides an overview of the existing literature on the subject of assessment and monitoring of tree roots and their interaction with the soil. An overview of tree root systems architecture is given, and the main issues in terms of health and stability of trees, as well as the impact of trees on the built environment, are discussed. An overview of the main destructive and non-destructive testing (NDT) methods is therefore given. The paper also highlights the lack of available research based outputs in the field of tree roots and soil interaction, as well as of the interconnectivity of tree roots with one another. Additionally, the effectiveness of non-destructive methods is demonstrated, in particular ground penetrating radar, in mapping tree root configurations and their interconnectivity. Furthermore, the paper references recent developments in estimating tree root mass density and health
Audit committee gender diversity and financial reporting: evidence from restatements
Get PDFPurpose – The main purpose of this study is to investigate the association between gender diversity on audit committees and the incidence of financial restatements.
Design/methodology/approach – Using a sample of 683 firm-year observations from Iranian listed companies for the period from 2013 to 2017, this paper uses a logistic regression model to examine a research hypothesis related to the association between the presence of female directors on the audit committee and the incidence of financial restatements.
Findings – After controlling for other restatement-related factors, we found that the presence of at least one female director on audit committees reduces the likelihood of the incidence of financial restatements. Robustness tests also confirmed this result. Moreover, we found that independent and financial expert female directors on audit committees are more strongly associated with a reduction in financial restatements. Finally, our additional analysis suggests that, in firms with gender diversity on audit committees and also the presence of independent and financial expert female directors, the likelihood of hiring auditors of a higher quality increases. Generally, the findings are consistent with the literature on gender diversity which suggests that women perform better in a monitoring role, are more conservative and make more ethical decisions.
Practical implications – The findings of this study could help with the understanding of broader participation of female directors on company boards and subgroups such as the audit committee, and of the improvement in corporate governance. Moreover, the findings can be of particular interest to monitoring authorities and policy makers in developing countries and send positive signals to them regarding the recommendation or requirement of gender diversity as a part of corporate governance mechanisms.
Originality/value – The present study contributes to the extant literature by providing empirical evidence on the effect of audit committee gender diversity on financial restatements. Furthermore, this study provides evidence on the more effective oversight and greater ability of independent female directors and financial expert female directors, respectively; which has been significantly disregarded in the previous studies
How do we experience crossmodal correspondent mulsemedia content?
Get PDFSensory studies emerged as a significant influence upon Human Computer Interaction and traditional multimedia. Mulsemedia is an area that extends multimedia addressing issues of multisensorial response through the combination of at least three media, typically a non-traditional media with traditional audio-video content. In this paper, we explore the concepts of Quality of Experience and crossmodal correspondences through a case study of different types of mulsemedia setups. The content is designed following principles of crossmodal correspondence between different sensory dimensions and delivered through olfactory, auditory and vibrotactile displays. The Quality of Experience is evaluated through both subjective (questionnaire) and objective means (eye gaze and heart rate). Results show that the auditory experience has an influence on the olfactory sensorial responses and lessens the perception of lingering odor. Heat maps of the eye gazes suggest that the crossmodality between olfactory and visual content leads to an increased visual attention on the factors of the employed crossmodal correspondence (e.g. colour, brightness and shape)
Self-assessed health status among ethnic elderly of tea garden workers in Bangladesh
Get PDFThe proportion of elderly has been increased gradually over the past years and this has created many causes for concerns particularly in individual’s health status. Relatively little is known about health status of older ethnic group across the world. The study aims to explore the health status of ethnic elderly among Tea Garden workers in Bangladesh. A total of 229 elderly were interviewed from different tea gardens. Prevalence ratio and adjusted prevalence ratio were calculated using simple and multiple Poisson regression analysis. The study revealed that more than 90% of the elderly had suffered from multi-morbidity. Gender, age, family behavior, number of meals in a day, taking milk or milk products and taking sugar were highly associated factor to lead healthy life for elderly. Female and unemployed elderly were in more risk to suffer from multi-morbidity, illiterate were also a risk factor for multi-morbidity but effected by confounding factors. An elderly who rated himself as unhealthy was 1.75 times more risk in compare to healthy elderly. In addition, the ethnic elderly who were suffering from difficulties of seeing, getting up, standing, remembering and others disability were in more risk of suffering from multi-morbidity
Proactive caching placement for arbitrary topology with multi-hop forwarding in ICN
Get PDFWith the rapid growth of network traffic and the enhancement of the quality of experiences of users, Information-Centric Networking (ICN), which is a content-centric network architecture with named data caching and routing, is proposed to improve the multimedia content distribution efficiency. In arbitrary topology, cache nodes and users are randomly distributed and connected, hence it is challenging to achieve an optimal caching placement under this situation. In this paper, we propose a caching placement algorithm for arbitrary topology in ICN. We formulate an optimization problem of proactive caching placement for arbitrary topology combined with multi-hop forwarding, with an objective to optimize the user delay and the load balancing level of the nodes simultaneously. Since the original problem is NP-hard, we solve the formulated caching placement problem in two sub-problems, content replica allocation subproblem and content replica placement sub-problem. First, in the content replica allocation sub-problem, the replica number of each content is obtained by utilizing the auction theory. Second, the replica number of each content is used as a constraint for the content replica placement sub-problem, which is solved by matching theory. The caching placement algorithm combined with multi-hop NRR forwarding maximizes the utilization of cache resources in order to achieve better caching performance. The numerical results show that significant hop count savings and load balancing level improvement are attainable via the proposed algorithm
Heritage tourism and authenticity: the case of Voroneț
Get PDFCulture is an essential component that adds to the attractiveness of a destination and contributes to the authenticity of an area through its ‘unique imprint on the cultural landscape’ Timothy, 2011, p. 58). To capitalize on this, cultural tourism has been proposed in many destinations as a path to economic prosperity, better job opportunities for locals and increased tax revenues.
This study focuses on heritage tourism, a popular choice among visitors and an area of research that has recently attracted increased attention from academics. Heritage is seen as one of the main tourism drivers for many regions, helping destinations to differentiate between one another in a very competitive environment. The literature on this form of tourism has expanded rapidly since the initial debates in the late ‘80s, with the topic being included by Cohen and Cohen (2012) among the current issues deserving further attention from researchers.
Additionally, the present work looks at the role that authenticity plays in tourist destinations, ‘an important attribute of heritage tourism […] or at least the perception of it’(Chhabra et al., 2003). While there is a wealth of research on authenticity and its applicability,this is mostly focused on Western countries. This research therefore contributes to filling this gap by exploring the applicability of the concept in a non-Western context, which it does by looking at the importance of the cultural landscape and traditional houses for the sustainable development of tourism in a heritage site from a former communist country in Eastern Europe. Specifically, the study focuses on objective authenticity and looks at the importance of preserving the built environment (i.e. traditional houses) for the sustainable development of tourism in the Voroneț area in Romania. Situated in the North-East of Romania, Voroneț is considered to be one of the main tourist attractions in the region of Bucovina, and one of the most important destinations for cultural, heritage and religious tourism in the country