The changing role of employees in service theory and practice over the last few decades is overviewed from the perspectives of the management and marketing disciplines. The criticality of employees, ...particularly front-line employees, in driving customer service outcomes was emphasized in both fields in the 1980s and 1990s. The rise of services marketing highlighted the role of employees in dyadic service encounters with customers. In management, the implications of the customer interface for employee and organization were developed. In the 2000s, the status of the employee's role appeared to diminish as service marketing theory shifted from a provider to a consumer perspective on customer value creation, and as technology substituting for employees grew in practice. In management, new theory and research directions on service employees essentially plateaued. Going forward in evolving service contexts, employees will fill roles as “Innovators”; “Differentiators”; “Enablers” and “Coordinators”. Suggestions are offered for what management can learn from services marketing in the pursuit of interdisciplinary research.
Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the ...viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the "class 3" epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.
Theory and research on service climate are synthesized, and an extensive agenda for future research is proposed. The service climate construct is first differentiated from conceptually related but ...distinct constructs, such as job satisfaction, service culture, and service orientation. Then a framework is presented based on prior research that displays service climate’s antecedents and consequences and the linkages among them. The synthesis draws heavily upon organizational behavior/human resource management (OB/HRM), but service climate has also received significant interdisciplinary attention. In particular, past work has integrated OB/HRM’s focus on the internal organization and marketing’s focus on the external world of the customer. The future research agenda includes further specification of the framework’s variables and linkages (e.g., the relative roles of individual and contextual attributes in creating service climate) as well as recommended research methods (e.g., profile analysis to assess interactions among multiple climates in a setting). Finally, the utility of the service climate framework for analyzing four key issues in service management is demonstrated: service infusion in manufacturing; the cocreation of value; sustainable competitive advantage; and the fostering of additional interdisciplinary research.
The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing ...antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.
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•Measured effects on folding and ACE2 binding of all mutations to the SARS-CoV-2 RBD•Provide open data and interactive visualization for vaccine design and surveillance•Identify constrained surfaces as ideal targets for vaccines and antibody therapeutics•Mutations that enhance ACE2 affinity exist but are not selected in pandemic isolates
Starr et al. systematically change every amino acid in the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and determine the effects of the substitutions on RBD expression, folding, and ACE2 binding. The work identifies structurally constrained regions of the spike RBD that would be ideal targets for COVID-19 countermeasures and demonstrates that mutations in the virus that enhance ACE2 affinity can be engineered but have not, to date, been naturally selected during the pandemic.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern evades antibody-mediated immunity that comes from vaccination or infection with earlier variants due to ...accumulation of numerous spike mutations. To understand the Omicron antigenic shift, we determined cryo-electron microscopy and x-ray crystal structures of the spike protein and the receptor-binding domain bound to the broadly neutralizing sarbecovirus monoclonal antibody (mAb) S309 (the parent mAb of sotrovimab) and to the human ACE2 receptor. We provide a blueprint for understanding the marked reduction of binding of other therapeutic mAbs that leads to dampened neutralizing activity. Remodeling of interactions between the Omicron receptor-binding domain and human ACE2 likely explains the enhanced affinity for the host receptor relative to the ancestral virus.
Hemolytic uremic syndrome (HUS) is major global health care issue as it is the leading cause of acute kidney injury in children. It is a triad of acute kidney injury, microangiopathic hemolytic ...anemia, and thrombocytopenia. In recent years, major advances in our understanding of complement-driven inherited rare forms of HUS have been achieved. However, in children 90% of cases of HUS are associated with a Shiga toxin-producing enteric pathogen. The precise pathological mechanisms in this setting are yet to be elucidated. The purpose of this review is to discuss advances in our understanding of the pathophysiology underlying HUS and identify the key questions yet to be answered by the scientific community.
The context in which service is delivered and experienced has, in many respects, fundamentally changed. For instance, advances in technology, especially information technology, are leading to a ...proliferation of revolutionary services and changing how customers serve themselves before, during, and after purchase. To understand this changing landscape, the authors engaged in an international and interdisciplinary research effort to identify research priorities that have the potential to advance the service field and benefit customers, organizations, and society. The priority-setting process was informed by roundtable discussions with researchers affiliated with service research centers and networks located around the world and resulted in the following 12 service research priorities:
stimulating service innovation,
facilitating servitization, service infusion, and solutions,
understanding organization and employee issues relevant to successful service,
developing service networks and systems,
leveraging service design,
using big data to advance service,
understanding value creation,
enhancing the service experience,
improving well-being through transformative service,
measuring and optimizing service performance and impact,
understanding service in a global context, and
leveraging technology to advance service.
For each priority, the authors identified important specific service topics and related research questions. Then, through an online survey, service researchers assessed the subtopics’ perceived importance and the service field’s extant knowledge about them. Although all the priorities and related topics were deemed important, the results show that topics related to transformative service and measuring and optimizing service performance are particularly important for advancing the service field along with big data, which had the largest gap between importance and current knowledge of the field. The authors present key challenges that should be addressed to move the field forward and conclude with a discussion of the need for additional interdisciplinary research.
SARS-CoV-2 is the causative agent of the COVID-19 pandemic, with 10 million infections and more than 500,000 fatalities by June 2020. To initiate infection, the SARS-CoV-2 spike (S) glycoprotein ...promotes attachment to the host cell surface and fusion of the viral and host membranes. Prefusion SARS-CoV-2 S is the main target of neutralizing antibodies and the focus of vaccine design. However, its limited stability and conformational dynamics are limiting factors for developing countermeasures against this virus. We report here the design of a construct corresponding to the prefusion SARS-CoV-2 S ectodomain trimer, covalently stabilized by a disulfide bond in the closed conformation. Structural and antigenicity analyses show we successfully shut S in the closed state without otherwise altering its architecture. We demonstrate that this strategy is applicable to other β-coronaviruses, such as SARS-CoV and MERS-CoV, and might become an important tool for structural biology, serology, vaccine design and immunology studies.
A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I in the signal peptide, W152C in the N-terminal ...domain (NTD), and L452R in the receptor-binding domain (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based messenger RNA vaccine or from convalescent individuals exhibited neutralizing titers that were reduced 2- to 3.5-fold against the B.1.427/B.1.429 variant relative to wild-type pseudoviruses. The L452R mutation reduced neutralizing activity in 14 of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 of 10 NTD-specific mAbs because the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and the formation of a new disulfide bond, as revealed by mass spectrometry and structural studies.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission leads to the emergence of variants, including the B.1.617.2 (Delta) variant of concern that is causing a new wave of ...infections and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing their immune evasion. Mutations in the B.1.617.1 (Kappa) and Delta spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including remodeling of the Delta amino-terminal domain. The angiotensin-converting enzyme 2 binding affinities of the Kappa and Delta receptor binding domains are comparable to the Wuhan-Hu-1 isolate, whereas B.1.617.2+ (Delta+) exhibits markedly reduced affinity.
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