ABSTRACT
Background: The recent global COVID-19 pandemic serves as another reminder that people in different urban neighborhoods need equal access to basic medical services. This study aims to improve the spatial accessibility of healthcare services toward the '15-minute city' goal. Methods: We chose Zhengzhou, China, as a case study. To improve spatial accessibility, two optimization models of optimal supply-demand allocation (OSD) and the capacitated p-medina problem (CPMP) were used. Spatial accessibility in this study is defined as the walking time from the communities to healthcare centers. Results: For the current status of healthcare services at the community level, the mean travel time is 18.3 min, and 39.6% of residents can access healthcare services within a 15-minute travel time. Population coverage within a 15-minute walking time is significantly lower than the national target of 80%. After redefining the service areas through OSD allocation, the mean travel time was reduced to 16.5 min, and 45.1% of the population could reach services. Furthermore, the 60 newly proposed healthcare centers selected by the CPMP model could potentially increase by 35.0% additional population coverage. The average travel time was reduced to 10 min. Conclusions: Both the redefinition of the service areas and the opening of new service centers are effective ways to improve the spatial accessibility of healthcare services. Two methods of this study have implications for urban planning practices towards the 15-minute city.
ABSTRACT
Consecutive glycosylation sites occur in both self and viral proteins. Glycan-shielding of underneath peptide region is a double-edged sword, that avoids immune attack to self-proteins, but helps viruses including HIV-1 and SARS-CoV2 to escape antibody binding. Here we report a high-affinity antibody, 16A, binding to linear peptide containing consecutive glycosylation sites. Co-crystallization of 16A Fab and glycopeptides with GalNAc modifications at different sites showed that STAPPAHG is the sequence recognized by 16A antibody. GalNAc modification at Threonine site on STAPPAHG sequence significantly increased the affinity of Fab binding by 30.6 fold (KD=6.7nM). The increased affinity is conferred by hydrophilic and pi-stacking interactions between the GalNAc residue on Threonine site and a Trp residue from the CDR1 region of the heavy chain. Furthermore, molecular modeling suggested that GalNAc on T site causes more favorable conformation for antibody binding. These results showed that glycan modification most proximal to linear peptide core epitope significantly increases antigenicity of a glycopeptide epitope. The antibody recognition mode by peptide-binding CDR groove with a glycan-binding edge, may shed light on designing of linear glycopeptide-based vaccines for cancer and viral diseases. Teaser A high-affinity antibody was found to bind densely glycosylated glycoprotein region by a peptide binding groove of the antibody’s variant region, with a glycan-binding edge specific to glycosylation site most proximal to core peptide epitope.