62 research outputs found
Integrity and Its Counterfeits: Implications for Economy, Business and Management
While the concept of integrity has long been explored by great philosophers and thinkers, its application in modern and postmodern business and economic contexts has been underdeveloped. Little have been done to address the vagueness and paradoxicality of integrity and its shadow reality of counterfeits. The thematic collection, which this paper complements, entitled ‘Integrity and Its Counterfeits: Implications for Economy, Business and Management’, makes a contribution towards filling the gap between the abstract concept of integrity and its application into business and economy, with a particular attention on the ambiguous, equivocal and diverse meanings of the concept, the complex and dynamic practicality of integrity, and the grey and dark areas of business out of integrity. This article introduces the background of the research theme and provides exemplary debates and emerging avenues of discussion on this topic
Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.
Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy
Community-acquired pneumonia related to intracellular pathogens
Community-acquired pneumonia (CAP) is associated with high rates of morbidity and mortality worldwide; the annual incidence of CAP among adults in Europe has ranged from 1.5 to 1.7 per 1000 population. Intracellular bacteria are common causes of CAP. However, there is considerable variation in the reported incidence between countries and change over time. The intracellular pathogens that are well established as causes of pneumonia are Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Chlamydophila psittaci, and Coxiella burnetii. Since it is known that antibiotic treatment for severe CAP is empiric and includes coverage of typical and atypical pathogens, microbiological diagnosis bears an important relationship to prognosis of pneumonia. Factors such as adequacy of initial antibiotic or early de-escalation of therapy are important variables associated with outcomes, especially in severe cases. Intracellular pathogens sometimes appear to cause more severe disease with respiratory failure and multisystem dysfunction associated with fatal outcomes. The clinical relevance of intracellular pathogens in severe CAP has not been specifically investigated. We review the prevalence, general characteristics, and outcomes of severe CAP cases caused by intracellular pathogens
Vaccination with poly(IC:LC) and peptide-pulsed autologous dendritic cells in patients with pancreatic cancer
Global Cryptoasset Regulatory Landscape Study
The first global comparative study of cryptoasset regulation by the Cambridge Centre for Alternative Finance provides a comprehensive, systematic, and comparative analysis of the current regulatory landscape of cryptoassets and related activities. The study covers 23 jurisdictions and is based on both desktop research and in-person interviews with regulators and policymakers. The report aims to compare and contrast various regulatory approaches and practices with regards to cryptoassets in a number of jurisdictions and shed light on current regulatory challenges and opportunities. The study serves as a practical and analytical tool for regulators, market participants, and other stakeholders in the cryptoasset ecosystem. Section 1 sets out a theoretical framework to conceptualise cryptoassets and related activities. It looks at three key aspects in a regulatory context: (1) the nature and form of cryptoassets, (2) the issuance of cryptoassets, and (3) intermediated activities in the life cycle of cryptoassets. A number of regulatory recommendations are brought forward. Section 2 provides a global comparative analysis of cryptoasset regulation in 23 jurisdictions. It examines regulatory authorities regulating cryptoassets, their current definition and classification of cryptoassets and related activities, as well as regulatory processes and responses (e.g. existing regulation, retrofitted regulation, bespoke regulation and bespoke regulatory regime). Section 3 highlights some of the most salient challenges and potential gaps that stem from the development and implementation of cryptoasset regulation. Section 4 consists of an in-depth analysis of cryptoasset regulations in 23 jurisdictions that constitute the backbone of the comparative analysis.</p
Infectious bronchitis virus: dominance of ArkDPI-type strains in the United States broiler industry during the last decade
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