Dry eye disease (DED) has high personal and societal costs, but its pathology remains elusive due to intertwined biophysical and biochemical processes at the ocular surface. Specifically, mucin deficiency is reported in a subset of DED patients, but its effects on ocular interfacial properties remain unclear. Herein a novel in vitro mucin‐deficient mimetic ocular surface (Mu‐DeMOS) with a controllable amount of membrane‐tethered mucin molecules is developed to represent the diseased ocular surfaces. Contact angle goniometry on mimetic ocular surfaces reveals that high surface roughness, but not the presence of hydrophilic mucin molecules, delivers constant hydration over native ocular surface epithelia. Live‐cell rheometry confirms that the presence of mucin‐like glycoproteins on ocular epithelial cells reduces shear adhesive strength at cellular interfaces. Together, optimal surface roughness and surface chemistry facilitate sustainable lubrication for healthy ocular surfaces, while an imbalance between them contributes to lubrication‐related dysfunction at diseased ocular epithelial surfaces. Furthermore, the restoration of low adhesive strength at Mu‐DeMOS interfaces through a mucin‐like glycoprotein, recombinant human lubricin, suggests that increased frictional damage at mucin‐deficient cellular surfaces may be reversible. More broadly, these results demonstrate that Mu‐DeMOS is a promising platform for drug screening assays and fundamental studies on ocular physiology.
Purpose
The purpose of this paper is to identify and rank supply chain disruption causes for Western buying firms in the Chinese market; to identify supplier-relationship-specific mitigation strategies to avoid and resist such disruptions; and to develop and propose a framework of relational supply chain disruption management with Chinese suppliers.
Design/methodology/approach
Two group exercises with 42 representatives from Western manufacturing buying firms and nine in-depth interviews were conducted. The group exercises applied the nominal group technique.
Findings
The authors identified and ranked 22 disruption causes in China for Western buying firms. Evaluating the five most urgent causes, 43 mitigation strategies could be identified that build on implementing strategic relationships with Chinese suppliers. A framework of relational supply chain disruption management for Western buying firms was developed with six propositions on primary constructs, mediators, and moderators, highlighting guanxi as a fundamental construct of relations within the Chinese culture.
Research limitations/implications
The findings contribute to theory development at the intersection of risk management and culture. Quantitative testing of the proposed relationships in the framework is needed to derive more reliable conclusions.
Practical implications
The study depicts how cultural differences between Chinese suppliers and Western buyers influence relational supply chain disruption management strategies. Using the study findings, managers of Western buying firms are informed regarding the most pressing disruption causes in the Chinese market and the value and strategic use of Chinese-supplier relationships.
Originality/value
The study provides a valuable contribution to the scant body of literature on disruption management in supply chains with Chinese suppliers. It contributes to our understanding of a successful risk management in the presence of cultural differences.
Patent expiration of first-generation biologics and the high cost of innovative biologics are 2 drivers for the development of biosimilar products. There are, however, technical challenges to the production of exact copies of such large molecules. In this study, we performed a head-to-head comparison between the originator anti-VEGF-A Fab product LUCENTIS® (ranibizumab) and an intended copy product using an integrated analytical approach. While no differences could be observed using size-exclusion chromatography, capillary electrophoresis-sodium dodecyl sulfate and potency assays, different acidic peaks were identified with cation ion exchange chromatography and capillary zone electrophoresis. Further investigation of the intact Fab, subunits and primary sequence with mass spectrometry demonstrated the presence of a modified light chain variant in the intended copy product batches. This variant was characterized with a mass increase of 27.01 Da compared to the originator sequence and its abundance was estimated in the range of 6–9% of the intended copy product light chain. MS/MS spectra interrogation confirmed that this modification relates to a serine to asparagine sequence variant found in the intended copy product light chain. We demonstrated that the integration of high-resolution and sensitive orthogonal technologies was beneficial to assess the similarity of an originator and an intended copy product.
Background: Digital supply chain twins (DSCT) are gaining increased attention in academia and practice as they emerge as one of the most important trends in logistics and supply chain management (LSCM). Still, there seems to be no common understanding of the term in scientific literature. Moreover, the broad field of LSCM allows for a multitude of feasible application areas and use cases, yet there exists no conclusive list of them as to date. Methods: This study builds upon a systematic literature review of 66 DSCT articles to identify application areas of DSCT in LSCM as well as specific use cases and their respective intended benefits. Results: To start with, the study derives a unified definition of DSCTs, including possible scopes of applications. Afterwards, five application areas of DSCT in LSCM are synthesized as well as 14 individual use cases and their respective intended benefits. Conclusions: The study leads towards a conceptual clarification of DSCT that is of importance for research and practice alike. For managers it additionally provides up-to-date use cases to guide DSCT applications in practice.
In recent years test systems have been described that may be applied routinely to discriminate between contact allergens and irritants in vitro. Using human monocyte-derived dendritic cells (MoDC), this study was designed to refine the settings of a potential routine screening protocol for contact allergens and to investigate the so far poorly defined concentration dependency of contact allergen-specific effects. MoDC were generated by 6 days of culture in the presence of IL-4 and GM-CSF and were then cultured for 24 or 48 h in medium with lipopolysaccharide (LPS), contact allergens [picrylsulphonic acid (TNBS), 1-chloro-2,4-dinitrobenzene (DNCB)] or irritants [sodium dodecyl sulphate (SDS), benzalkonium chloride (BAC)] that were free of detectable endotoxin contamination. The induction of CD86 and HLA-DR expression was quantified by flow cytometry as markers for MoDC activation. LPS activation upregulated CD86 about 20-fold and HLA-DR expression about 4-fold. Compared to LPS, contact allergens had weaker effects. TNBS and DNCB induced activation marker upregulation starting slightly below the cytotoxic concentration and increasing in a dose-dependent manner. However, at partially cytotoxic concentrations, irritants also induced CD86 and HLA-DR expression, as confirmed by flow cytometry and quantitative RT-PCR. Both SDS and BAC induced activation marker expression on surviving MoDC, when more than 50% of the MoDC population had been killed by the treatment. Consequently, routine testing of unknown substances would need to quantify activation marker expression as well as cytotoxicity in parallel. In the concentration range around the lowest cytotoxic concentration, the assay may be able to discriminate between contact allergens and irritants.
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