Large-scale urban regeneration threatening historic urban landscapes. The Liverpool Waters development and the loss of a UNESCO World Heritage Site.

The city of Liverpool has undergone repeated processes of urban transformation and urban regeneration over the last half a century. The city has been a test bed for urban experimentation with mass clearance, housing, and relocation schemes in the 1970s followed by culture, event, and heritage-based regeneration strategies from the 1980s through 2000s. Following the perceived success of the 2008 European Capital of Culture and city centre Liverpool One development, an even larger, longer-term, and more expensive development was proposed – Liverpool Waters. Yet unlike its antecedents, which were consciously woven into existing urban fabric and combined multiple strategies and funding schemes simultaneously, the Liverpool Waters approach envisioned a tabula rasa disconnected from its surrounding context and which would also introduce new building typologies to the city – the skyscraper. This article examines the long-term history of urban regeneration in the city and nearly ten-year process of negotiations and redesigns of Liverpool Waters that ultimately led to the deletion of the Liverpool - Maritime Mercantile City site from UNESCO’s World Heritage List. This case provides valuable lessons for cities seeking to implement large-scale urban regeneration schemes and the need for strategic and contextually sensitive approaches

VEGF (Vascular Endothelial Growth Factor) Induces NRP1 (Neuropilin-1) Cleavage via ADAMs (a Disintegrin and Metalloproteinase) 9 and 10 to Generate Novel Carboxy- Terminal NRP1 Fragments That Regulate Angiogenic Signaling

OBJECTIVE: NRP1(neuropilin-1) acts as a coreceptor for VEGF (vascular endothelial growth factor) with an essential role in angiogenesis. Recent findings suggest that posttranslational proteolytic cleavage of VEGF receptors may be an important mechanism for regulating angiogenesis, but the role of NRP1 proteolysis and the NRP1 species generated by cleavage in endothelial cells is not known. To characterize NRP1 proteolytic cleavage in endothelial cells, determine the mechanism, and investigate the role of NRP1 cleavage in regulation of endothelial cell function. APPROACH AND RESULTS: NRP1 species comprising the carboxy (C)-terminal and transmembrane NRP1 domains but lacking the ligand-binding A and B regions are constitutively expressed in endothelial cells. Generation of these C-terminal domain NRP1 proteins is upregulated by phorbol ester and Ca2+ ionophore, and reduced by pharmacological inhibition of metalloproteinases, by small interfering RNA-mediated knockdown of 2 members of ADAM (a disintegrin and metalloproteinase) family, ADAMs 9 and 10, and by a specific ADAM10 inhibitor. Furthermore, VEGF upregulates expression of these NRP1 species in an ADAM9/10-dependent manner. Transduction of endothelial cells with adenoviral constructs expressing NRP1 C-terminal domain fragments inhibited VEGF-induced phosphorylation of VEGFR2 (VEGF receptor tyrosine kinase)/KDR and decreased VEGF-stimulated endothelial cell motility and angiogenesis in coculture and aortic ring sprouting assays. CONCLUSIONS: These findings identify novel NRP1 species in endothelial cells and demonstrate that regulation of NRP1 proteolysis via ADAMs 9 and 10 is a new regulatory pathway able to modulate VEGF angiogenic signaling

Evolution of seismicity near the southernmost terminus of the San Andreas Fault: Implications of recent earthquake clusters for earthquake risk in southern California

Three earthquake clusters that occurred in the direct vicinity of the southern terminus of the San Andreas Fault (SAF) in 2001, 2009, and 2016 raised significant concern regarding possible triggering of a major earthquake on the southern SAF, which has not ruptured in more than 320 years. These clusters of small and moderate earthquakes with M ≤ 4.8 added to an increase in seismicity rate in the northern Brawley seismic zone that began after the 1979 M_w 6.5 Imperial Valley earthquake, in contrast to the quiet from 1932 to 1979. The clusters so far triggered neither small nor large events on the SAF. The mostly negative Coulomb stress changes they imparted on the SAF may have reduced the likelihood that the events would initiate rupture on the SAF, although large magnitude earthquake triggering is poorly understood. The relatively rapid spatial and temporal migration rates within the clusters imply aseismic creep as a possible driver rather than fluid migration

Wind Tunnel Results of the Aerodynamic Performance of a 1/8-Scale Model of a Twin-Engine Transport with Multi-Element Wing

A wind tunnel investigation was performed in the 14- by 22-Foot Subsonic Tunnel on a pressure instrumented 1/8-scale twin-engine subsonic transport to better understand the flow physics on a multi-element wing section. The wing consisted of a part-span, triple-slotted trailing edge flap, inboard leading-edge Krueger flap and an outboard leading-edge slat. The model was instrumented with flush pressure ports at the fuselage centerline and seven spanwise wing locations. The model was tested in cruise, take-off and landing configurations at dynamic pressures and Mach numbers from 10 lbf/ft(exp 2) to 50 lbf/ft(exp 2) and 0.08 to 0.17, respectively. This resulted in corresponding Reynolds numbers of 0.8 x 10(exp 5) to 1.8 x 10(exp 6). Pressure data were collected using electronically scanned pressure devices and force and moment data were collected with a six component strain gauge balance. Results are presented for various control surface deflections over an angle-of-attack range from -4 degrees to 16 degrees and sideslip angle range from -10 degrees to 10 degrees. Longitudinal and lateral directional aerodynamic data are presented as well as chordwise pressure distributions at the seven spanwise wing locations and the fuselage centerline

Urban heritage fragility and antifragility:Matera and the 2019 European Capital of Culture

The city of Matera is known internationally for its prehistoric built heritage and for being the oldest continuously inhabited city in Europe. Until the Covid-19 pandemic, the heritage area of the “Sassi” used to attract significant numbers of tourists and day-trippers. This exerted significant pressure on this fragile part of the city. The plans for the Matera-Basilicata 2019 European Capital of Culture (ECoC) included measures that focused on the Sassi and others that intended to expand the set of heritage and cultural attractions in other parts of the city, as well as to strengthen the social and economic system of Matera as an innovation hub for the region. While the mega-event planning and delivery improved accessibility, public spaces and the local cultural economy, the ECoC did not significantly and directly reduce the fragility of the city’s heritage. This contribution discusses the relationship between urban heritage and mega-event policies and discusses it in the light of a fragility/antifragility theoretical framework

Subsonic aerodynamic characteristic of semispan commercial transport model with wing-mounted advanced ducted propeller operating in reverse thrust

A test was conducted in the Langley 14 by 22 Foot Subsonic Tunnel to determine the effect of the reverse-thrust flow field of a wing-mounted advanced ducted propeller on the aerodynamic characteristics of a semispan subsonic high-lift transport model. The advanced ducted propeller (ADP) model was mounted separately in position alongside the wing so that only the aerodynamic interference of the propeller and nacelle affected the aerodynamic performance of the transport model. Mach numbers ranged from 0.14 to 0.26; corresponding Reynolds numbers ranged from 2.2 to 3.9 x 10(exp 6). The reverse-thrust flow field of the ADP shielded a portion of the wing from the free-stream airflow and reduced both lift and drag. The reduction in lift and drag was a function of ADP rotational speed and free-stream velocity. Test results included ground effects data for the transport model and ADP configuration. The ground plane caused a beneficial increase in drag and an undesirable slight increase in lift. The ADP and transport model performance in ground effect was similar to performance trends observed for out of ground effect. The test results form a comprehensive data set that supports the application of the ADP engine and airplane concept on the next generation of advanced subsonic transports. Before this investigation, the engine application was predicted to have detrimental ground effect characteristics. Ground effect test measurements indicated no critical problems and were the first step in proving the viability of this engine and airplane configuration

Molecular recording of mammalian embryogenesis.

Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes

Novel Enhanced Recovery After Surgery Pathway Reduces Length of Stay and Postoperative Opioid Usage in Adolescent Idiopathic Scoliosis Patients Undergoing Posterior Spinal Fusion

Purpose: The goal of this study was to compare our institution’s recently implemented enhanced recovery after surgery (ERAS) protocol to previous post-operative management for adolescent idiopathic scoliosis patients undergoing posterior spinal fusion, specifically assessing length of stay, opioid consumption, and pain scores. Methods: This is a retrospective analysis that compares the length of stay, opioid consumption, and pain scores of patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis. Patients were analyzed prior to the implementation of our ERAS protocol, deemed the traditional pain pathway (TPP), to those who underwent the ERAS pathway. All patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis were included. Patients were excluded if they weighed less than 40kg, had significant comorbidities, or had non-idiopathic causes of scoliosis. Results: We examined 22 patients in the TPP cohort and 20 in the ERAS cohort. Length of stay in the ERAS cohort was significantly reduced compared to the TPP by 1.7 days (P\u3c0.01). Overall opioid consumption was also significantly reduced in the ERAS with 1.4 ± 0.7 morphine equivalents (ME)/kg compared to the TPP 2.4 ± 1.1 ME/kg (P \u3c 0.01). We found no difference in pain scores between the two groups. Conclusion: Implementation of an ERAS pathway at our institution significantly reduced length of stay and opioid consumption in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion. These outcomes reduce morbidity and costs associated with posterior spinal fusion and provide an overall improvement in the quality of care for our patients