Highlights d Unmodified circRNA adjuvant induces antigen-specific T and B cell responses d m 6 A RNA modification marks self circRNAs and abrogates circRNA immunity d Unmodified circRNA and K63-polyubiquitin activate RIG-I and innate immune signaling d YTHDF2 binding of m 6 A-circRNA additionally suppresses circRNA immunity

Vaccines aim to elicit a robust, yet targeted, immune response. Failure of a vaccine to elicit such a response arises in part from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune system’s natural response to extended pathogen exposure during infection by designing an easily administered slow-delivery vaccine platform. We utilized an injectable and self-healing polymer–nanoparticle (PNP) hydrogel platform to prolong the codelivery of vaccine components to the immune system. We demonstrated that these hydrogels exhibit unique delivery characteristics, whereby physicochemically distinct compounds (such as antigen and adjuvant) could be codelivered over the course of weeks. When administered in mice, hydrogel-based sustained vaccine exposure enhanced the magnitude, duration, and quality of the humoral immune response compared to standard PBS bolus administration of the same model vaccine. We report that the creation of a local inflammatory niche within the hydrogel, coupled with sustained exposure of vaccine cargo, enhanced the magnitude and duration of germinal center responses in the lymph nodes. This strengthened germinal center response promoted greater antibody affinity maturation, resulting in a more than 1000-fold increase in antigen-specific antibody affinity in comparison to bolus immunization. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of subunit vaccines.

Customers select suppliers based on the relative importance of different attributes such as quality, price, flexibility, and delivery performance. This study examines the difference between managers' rating of the perceived importance of different supplier attributes and their actual choice of suppliers in an experimental setting. We use two methods: a Likert scale set of questions, to determine the importance of supplier attributes; and a discrete choice analysis (DCA) experiment, to examine the choice of suppliers. The results indicate that although managers say that quality is the most important attribute for a supplier, they actually choose suppliers based largely on cost and delivery performance.

Purpose Purpose: The purpose of this paper is to understand the impact service innovation has on customers' choices within the hotel and leisure industry. The paper also discusses the influence of the creation of new services on both service development and operational strategy. Design/methodology/approach Design/methodology/approach: The analysis is based on a national survey of approximately 1,000 travelers in the United States, using a web-based data acquisition approach. The travelers are segmented by reason of travel (business or leisure), and discrete choice analysis is applied to model customer preferences for various hotel service innovations. Findings Findings: Overall, the study finds that service innovation does matter when guests are selecting a hotel, with type of lodging having the largest impact on a customer's hotel choice. In addition, service innovation is found to have a larger influence on choices when guests are staying at economy hotels rather than midrange to up-scale hotels. Also, leisure travelers were found to be more influenced by innovative amenities such as childcare programs and in-room kitchenettes than business travelers. Practical implications Practical implications: The understanding of customers' choices allows managers to better design their service offerings and formulate corresponding operational strategies around customer needs. Originality/value Originality/value: This paper examines the addition of innovation to the hotel service concept and is an excellent tool for managers deciding on which innovations to implement.

Research in the area of operations strategy has made significant progress during the past decade in terms of quantity of articles published, as well as the quality of these articles. Recent studies have examined the published literature base and determined that, in general, the field has progressed beyond an exploratory stage to a point where there is a core set of basic terminology and models. Concurrent with the formation and solidification of a core terminology, there is an increasing emphasis on developing and employing a set of reliable, valid, and reproducible methods for conducting research on operations strategy. We provide a review of common methods for assessing the degree of reliability and agreement of the responses provided by multiple raters within a given organization to a set of qualitative questions. In particular, we examine four methods of determining whether there is evidence of disagreement or bias between multiple raters within a single organization in a mail survey.

Despite the success of the BNT162b2 mRNA vaccine, the immunological mechanisms that underlie its efficacy are poorly understood. Here we analyzed the innate and adaptive responses to BNT162b2 in mice, and show that immunization stimulated potent antibody and antigen-specific T cell responses, as well as strikingly enhanced innate responses after secondary immunization, which was concurrent with enhanced serum interferon (IFN)-γ levels 1 d following secondary immunization. Notably, we found that natural killer cells and CD8 + T cells in the draining lymph nodes are the major producers of this circulating IFN-γ. Analysis of knockout mice revealed that induction of antibody and T cell responses to BNT162b2 was not dependent on signaling via Toll-like receptors 2, 3, 4, 5 and 7 nor inflammasome activation, nor the necroptosis or pyroptosis cell death pathways. Rather, the CD8 + T cell response induced by BNT162b2 was dependent on type I interferon-dependent MDA5 signaling. These results provide insights into the molecular mechanisms by which the BNT162b2 vaccine stimulates immune responses.

The offshoring of knowledge services has become the stuff of newspaper headlines and U.S. presidential debates. Here, we view the antecedents of the current state of affairs. In the 1980s services offshoring was a trivial portion of the economy, but the seeds of today's situation were planted then. A combination of U.S. government neglect, foreign government activism, a culture change among business people concerning service processes, technological advances, and cultural relationships among countries have created the specific services offshoring configuration of today. #

Purpose Purpose-The application of self-service technology in transaction-based e-service (e.g. online financial services) creates a challenge for firms: what combination of features should they offer to satisfy needs from different customer segments? This paper seeks to address the above question by highlighting similarities and differences of consumer preferences among self-service, hybrid service and professional service segments for online financial services. Design/methodology/approach Design/methodology/approach-This study employs a web-based discrete choice experiment, in which 1,319 consumers were offered different account alternatives, which include features for self-service and professional assistance, price per transaction, and promotion offers. Findings Findings-The results demonstrate that overall, consumer preferences for features of online financial services differ across segments. Moreover, with the variation in the strength of self-reliance, interesting trends regarding the relative importance of features are observed. With the given customer segments, this study also identifies several demographic features with significant effects on the choice of service alternatives through a multinomial logistic model. Originality/value Originality/value-The authors believe that these results have both managerial and research implications for design and operations strategy formulation for online financial services.