Gated communities: Definitions, causes and consequences

Gated communities became an 'object of study' in the 1990s as social scientists observed their growth in several cities; they are now a feature of the urban landscape in most cities around the world. The expansion of gated communities has led to prolific research, examining different aspects of this type of residential development and providing evidence from case studies worldwide. This paper reviews how gated communities are conceptualised according to the literature and identifies the main factors influencing their development. It also considers spatial, economic, political and social consequences of the development of gated communities. These elements should be taken into account by planners and policymakers to minimise their negative impacts and maximise the positive consequences of a residential option that is likely to be part of the urban landscape for a long time

Mechanistic insight into RET kinase inhibitors targeting the DFG-out conformation in RET-rearranged cancer

Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. Here, we provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors such as AD80 or ponatinib that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells we identify the CCDC6-RETI788N mutation and drug-induced MAPK pathway reactivation as possible mechanisms, by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors

MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I

Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated inflammatory response in tumors that undergo stemness- and senescence-associated reprogramming. In these tumor cells, activation of the innate immunity sensor RIG-I via its agonist IVT4, triggers an interferon and a pro-apoptotic response that synergize with concomitant kinase inhibition. In humanized lung cancer xenografts and a syngeneic Egfr-driven lung cancer model these effects translate into reduction of exhausted CD8(+) T cells and robust tumor shrinkage. Overall, the mechanistic understanding of MAPK/IRF1-mediated intratumoral reprogramming may ultimately prolong the efficacy of targeted drugs in genetically defined cancer patients

MAPK-pathway inhibition mediates inflammatory reprogramming and sensitizes tumors to targeted activation of innate immunity sensor RIG-I.

Kinase inhibitors suppress the growth of oncogene driven cancer but also enforce the selection of treatment resistant cells that are thought to promote tumor relapse in patients. Here, we report transcriptomic and functional genomics analyses of cells and tumors within their microenvironment across different genotypes that persist during kinase inhibitor treatment. We uncover a conserved, MAPK/IRF1-mediated inflammatory response in tumors that undergo stemness- and senescence-associated reprogramming. In these tumor cells, activation of the innate immunity sensor RIG-I via its agonist IVT4, triggers an interferon and a pro-apoptotic response that synergize with concomitant kinase inhibition. In humanized lung cancer xenografts and a syngeneic Egfr-driven lung cancer model these effects translate into reduction of exhausted CD8+ T cells and robust tumor shrinkage. Overall, the mechanistic understanding of MAPK/IRF1-mediated intratumoral reprogramming may ultimately prolong the efficacy of targeted drugs in genetically defined cancer patients

Observations of forest stand top height and mean height from interferometric SAR and LIDAR over a conifer plantation at Thetford Forest, UK

Estimates of forest stand mean height using airborne LiDAR (light detection and ranging) instruments have been reported previously with accuracies comparable to traditional ground-based measurements. However, the small area covered by a LiDAR sensor in a single aircraft overpass is a significant hindrance for large-scale forest inventories. In comparison, airborne interferometric synthetic aperture radar (InSAR) systems are also able to make estimates of surface height, but the swath coverage is often far greater, typically five or ten times that of the LiDAR coverage. A set of interferometric data takes was acquired by the ESAR airborne sensor over a managed pine plantation at Thetford Forest, UK. Scattering phase centre height estimates were made from two single-pass X-band acquisitions and polarimetric repeat-pass L-band acquisitions and compared with height estimates made from a separate LiDAR acquisition. The relationship between the scattering phase centre heights and stand top heights estimated, and the accuracy of stand top height estimates estimated from InSAR and LiDAR is quantified by the root mean square error (rmse). General yield class models by the Forestry Commission (UK) were used to estimate stand top height from a GIS database used for forest management. The longer wavelength L-band radiation penetrates deeper into the canopy than the X-band, and the scattering phase centre height is affected by both forest structural parameters (canopy density, understorey, and gaps) and sensor parameters (look-angle and reduced coherence through temporal and volume decorrelation). Consequently, a simple translation of scattering phase centre height into stand top height gives noisy results for L-band, with observed rmse values between ±3.1 m in the near-range and ±6.4 m in the far-range. The X-band based top height estimates are more accurate, with rmse between ±2.9 m in the near- and ±4.1 m in the far-range, which can be further reduced by an empirical incidence angle correction. Stand top height estimates from LiDAR achieved an rmse of only ±2.0 m. The X-band scattering phase centre heights have also been related to mean stand height and are comparable with heights observed from the LiDAR sensor and field measurements. An rmse of ±2.5 m for the mean stand height estimates based on the X-band dataset was found. Finally, we briefly discuss error propagation from the use of a terrain model, here provided by the Ordnance Survey