893 research outputs found
DAPSONE INDUCED DRESS: A CASE REPORT
Drug reaction with eosinophilia and systemic symptoms. is a very dangerous adverse drug effect causing rashes, eosinophilia, and multiple organ damage. Many drugs are implicated in causing DRESS with most common ones being antimicrobials and antiepileptics. Dapsone used in the treatment of Hansen's disease as a first-line agent is known for causing many side effects ranging from nausea, vomiting, insomnia, anaphylaxis, hypersensitivity reactions, rashes, muscle weakness, abdominal pain, and so on. Hence, we report a rare case of dapsone-induced DRESS in a tertiary care hospital in South India.Â
Combinatorial multivalent interactions drive cooperative assembly of the COPII coat
Protein secretion is initiated at the endoplasmic reticulum by the COPII coat, which self-assembles to form vesicles. Here, we examine the mechanisms by which a cargo-bound inner coat layer recruits and is organized by an outer scaffolding layer to drive local assembly of a stable structure rigid enough to enforce membrane curvature. An intrinsically disordered region in the outer coat protein, Sec31, drives binding with an inner coat layer via multiple distinct interfaces, including a newly defined charge-based interaction. These interfaces combinatorially reinforce each other, suggesting coat oligomerization is driven by the cumulative effects of multivalent interactions. The Sec31 disordered region could be replaced by evolutionarily distant sequences, suggesting plasticity in the binding interfaces. Such a multimodal assembly platform provides an explanation for how cells build a powerful yet transient scaffold to direct vesicle traffic
Characterising Inter-helical Interactions of G Protein-Coupled Receptors with the Fragment Molecular Orbital Method
G-protein coupled receptors (GPCRs) are the largest superfamily of membrane proteins, regulating almost every aspect of cellular activity and serving as key targets for drug discovery. We have identified an accurate and reliable computational method to characterise the strength and chemical nature of the inter-helical interactions between the residues of transmembrane (TM) domains during different receptor activation states, something that cannot be characterised solely by visual inspection of structural information. Using the fragment molecular orbital (FMO) quantum mechanics method to analyse 35 crystal structures representing different branches of the class A GPCR family, we have identified 69 topologically-equivalent TM residues that form a consensus network of 51 inter-TM interactions, providing novel results that are consistent with and help to rationalise experimental data. This discovery establishes a comprehensive picture of how defined molecular forces govern specific inter-helical interactions which, in turn, support the structural stability, ligand binding and activation of GPCRs
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Strategic orientation, strategic renewal, and the international performance of born global firms
Copyright © Crown / The Author(s) 2023. The international business environment is both dynamic and turbulent. Accordingly, a new venture’s strategic orientation (SO) and ability to undertake strategic renewal (SR) are of great importance to its survival, growth and international performance. Building on the dynamic capability perspective, we explore how SR capability mediates the relationship between SO and the performance of mature born global firms (BGFs). In particular, we examine the direct and indirect interplay between the SO of BGFs and their performance outcomes. We use a sample of 195 export-oriented BGFs, derived from the Bangladeshi apparel industry. We use a hierarchical regression analysis technique to test the direct effects. The mediation effect is examined using three statistical tests – Baron and Kenney’s (1986) causal steps approach, the Sobel test, and the Hayes indirect effect with bootstrapping method – to ensure the validity and reliability of our findings. The results reveal a positive association between SO and the performance of BGFs, and that this relationship is mediated by the firms’ SR capability. We contribute to a greater understanding of the drivers of mature BGFs’ international performance by demonstrating a direct link between their SO and SR capability, which in turn affects their performance outcomes
Technology upgrading through co-creation of value in developing societies: Analysis of the mobile telephone industry in Bangladesh
The use of various forms of ICTs (information communication technology) such as mobile telephones can foster the socio-economic progression of developing countries. Contextually appropriate design and use are needed for ICTs to deliver value to various parties within the socio-economic spheres of developing countries who have different needs and wants compared to those of the developed world. There is however scant empirical evidence of how various stakeholders symbiotically interact and create value in developing countries where large multinationals have limited access and engagement. Drawing on the theoretical lens of co-creation of value our paper examines how technology upgrading is achieved in the context of the Bangladeshi mobile telephone industry. In doing so this paper suggests technology upgrading can be achieved even without some of the key prerequisites such as financial, institutional, infrastructural facilities cited in existing literature. The findings offer useful theoretical and policy implications by providing deeper understanding of the interactions and inter-relationships of those who have involvement in the value creation for mobile telephony and contribute to the development of effective business models and technological innovations for these marketplaces
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Brexit or Brand it? The Effects of Attitude Towards Brexit and Reshored Brands on Consumer Purchase Intention
Copyright © 2022 The Authors. Brexit has caused a seismic shift in the British socio-economic and political landscapes, creating widespread uncertainties, while simultaneously giving hope and national pride to millions. The decision by a number of organizations to reshore their production has opened a new era for business management that challenges the axiomatic assumption of the benefits of offshored production. Although reshoring predates Brexit, the link between the two in the British context is not just serendipitous and they are argued to have reasonable interlinkages. However, there is inadequate empirical evidence to suggest that British consumers’ attitude towards Brexit has any effect on their intention to purchase reshored brands. Through a mixed-methods study comprising a survey of 415 respondents and 20 in-depth interviews, this paper addresses this research gap. Findings suggest that corporate social responsibility (CSR) and consumer reshoring sentiment (CRS) have positive effects on consumers’ attitude towards reshored brands. Despite CRS's positive influence on attitude towards Brexit, the latter does not have any significant effects on the intention to purchase a reshored brand, which is positively influenced by the attitude towards the same brand. As such, companies should enhance the image of their brands and CSR in order to harness the benefits of reshoring.University of Western Australia, as part of the Wiley – The University of Western Australia agreement via the Council of Australian University Librarians
Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.
Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology
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Sustainability starts from within: A critical analysis of internal marketing in supporting sustainable value co-creation in B2B organisations
Data availability: The data used is confidential.Copyright © 2023 The Authors. The role of value co-creation in embedding sustainability within B2B marketing is well-documented. However, little is known about how employees enact this value co-creation, or how they can be supported to do so by their organisations. This article addresses this theoretical gap by analysing the role of employees and Internal Marketing in B2B organisations' efforts to co-create sustainable value. We propose that, since employees are tasked with delivering their organisation's ‘promise’, they can also purposely generate value for a broader range of stakeholders. As such, Internal Marketing can be a key enabler (or inhibitor) in these efforts. Adopting a Service-Dominant Logic and Service Gap lens, the research utilises Template Analysis of 17 semi-structured interviews with employees from a range of B2B organisations, which have adopted ‘sustainability-oriented’ practices. The findings highlight the contribution of Internal Marketing in supporting sustainable value, and demonstrate that, whilst employees can play a key role in the co-creation of sustainable value, value co-destruction can occur due to a ‘Sustainability gap’ within their organisations. This study contributes significantly to extant knowledge by offering a taxonomized analysis of the ‘sustainability gap’ and identifying how B2B organisations can address these at the awareness, design, internal communication, and implementation stages
Refining transcriptional regulatory networks using network evolutionary models and gene histories
<p>Abstract</p> <p>Background</p> <p>Computational inference of transcriptional regulatory networks remains a challenging problem, in part due to the lack of strong network models. In this paper we present evolutionary approaches to improve the inference of regulatory networks for a family of organisms by developing an evolutionary model for these networks and taking advantage of established phylogenetic relationships among these organisms. In previous work, we used a simple evolutionary model and provided extensive simulation results showing that phylogenetic information, combined with such a model, could be used to gain significant improvements on the performance of current inference algorithms.</p> <p>Results</p> <p>In this paper, we extend the evolutionary model so as to take into account gene duplications and losses, which are viewed as major drivers in the evolution of regulatory networks. We show how to adapt our evolutionary approach to this new model and provide detailed simulation results, which show significant improvement on the reference network inference algorithms. Different evolutionary histories for gene duplications and losses are studied, showing that our adapted approach is feasible under a broad range of conditions. We also provide results on biological data (<it>cis</it>-regulatory modules for 12 species of <it>Drosophila</it>), confirming our simulation results.</p
Non-standard interactions versus non-unitary lepton flavor mixing at a neutrino factory
The impact of heavy mediators on neutrino oscillations is typically described
by non-standard four-fermion interactions (NSIs) or non-unitarity (NU). We
focus on leptonic dimension-six effective operators which do not produce
charged lepton flavor violation. These operators lead to particular
correlations among neutrino production, propagation, and detection non-standard
effects. We point out that these NSIs and NU phenomenologically lead, in fact,
to very similar effects for a neutrino factory, for completely different
fundamental reasons. We discuss how the parameters and probabilities are
related in this case, and compare the sensitivities. We demonstrate that the
NSIs and NU can, in principle, be distinguished for large enough effects at the
example of non-standard effects in the --sector, which basically
corresponds to differentiating between scalars and fermions as heavy mediators
as leading order effect. However, we find that a near detector at superbeams
could provide very synergistic information, since the correlation between
source and matter NSIs is broken for hadronic neutrino production, while NU is
a fundamental effect present at any experiment.Comment: 32 pages, 5 figures. Final version published in JHEP. v3: Typo in Eq.
(27) correcte
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