Urban Morphology and Qualitative Topology: Open Green Spaces in High-Rise Residential Developments

High-rise housing complexes (HRHCs) are a prominent trend in urban development. They generate new configurations of open green spaces, thus creating a new set of human-environment relations and a new constellation of urban landscapes. However, little attention has been devoted by the literature to these new spatial configurations and the urban experience they offer. Focusing on the spaces between buildings, this research article examines the urban morphology of these large urban developments and how they are being experienced by residents. Based on morphological analysis, we propose a set of outputs with which to discern and evaluate various characteristics of these new spaces. Namely, a typology of HRHCs complexes, three evaluation indexes, and a green/gray nolli map. Drawing on morphological analysis, the research discusses the role of green spaces of HRHCs in the experience of residents. We portray different tensions arising from the residents’ experience based on walking interviews and propose how these tensions are connected to the morphology of space. Juxtaposing the morphological and qualitative topological analyses, we focus on the way that different planning aspects of HRHCs’ open spaces might foster everyday use and function as well as attitudes and feelings

Development of Novel Promiscuous Anti-Chemokine Peptibodies for Treating Autoimmunity and Inflammation

Chemokines and their receptors play critical roles in the progression of autoimmunity and inflammation. Typically, multiple chemokines are involved in the development of these pathologies. Indeed, targeting single chemokines or chemokine receptors has failed to achieve significant clinical benefits in treating autoimmunity and inflammation. Moreover, the binding of host atypical chemokine receptors to multiple chemokines as well as the binding of chemokine-binding proteins secreted by various pathogens can serve as a strategy for controlling inflammation. In this work, promiscuous chemokine-binding peptides that could bind and inhibit multiple inflammatory chemokines, such as CCL2, CCL5, and CXCL9/10/11, were selected from phage display libraries. These peptides were cloned into human mutated immunoglobulin Fc-protein fusions (peptibodies). The peptibodies BKT120Fc and BKT130Fc inhibited the ability of inflammatory chemokines to induce the adhesion and migration of immune cells. Furthermore, BKT120Fc and BKT130Fc also showed a significant inhibition of disease progression in a variety of animal models for autoimmunity and inflammation. Developing a novel class of antagonists that can control the courses of diseases by selectively blocking multiple chemokines could be a novel way of generating effective therapeutics

In vitro and in vivo therapeutic efficacy of CXCR4 antagonist BKT140 against human non–small cell lung cancer

ObjectivesCXCR4/CXCL12 interactions promote non–small cell lung cancer (NSCLC) growth and dissemination. Furthermore, this axis might promote NSCLC resistance to chemotherapy and/or radiotherapy. Therefore, the CXCR4/CXCL12 axis constitutes an attractive therapeutic target for the treatment of NSCLC. We aimed to characterize the therapeutic efficacy of the novel CXCR4 antagonist BKT140 against human NSCLC.MethodsWe determined the CXCR4 expression in 5 NSCLC cell lines (H358, A549, H460, H1299, and L4). We then tested the colony-forming capacity and proliferation of these cells in the presence of CXCL12 and BKT140. Next, we measured the in vivo growth of A549 and H460 xenografts with or without BKT140 treatment. Finally, we examined, in vitro, the potential antiproliferative effect of BKT140 combined with cisplatin or paclitaxel and after irradiation of NSCLC cells.ResultsAll tested cell lines expressed CXCR4 and showed increased colony formation in response to CXCL12 stimulation. BKT140 reduced the colony-forming capacity of NSCLC cells. Proliferation assays demonstrated both cytotoxic and cytostatic properties for this peptide. H460 cells were the most sensitive to BKT140 and A549 cells the least. Subcutaneous administration of BKT140 significantly delayed the development of H460 xenografts and showed a similar trend for A549 xenografts. Finally, the antiproliferative effects of BKT140 appears to be additive to those of chemotherapeutic drugs and radiotherapy.ConclusionsTargeting the CXCL12/CXCR4 axis with BKT140 attenuated NSCLC cells tumor growth and augmented the effects of chemotherapy and radiotherapy. Future research will benefit from delineating the downstream mechanism of BKT140 action and defining BKT140 susceptibility markers