The ‘Nordstrom Tower’: a landmark daylight injury study

This paper describes a landmark daylight injury study whereby measures predicted using climate-based daylight modelling formed part of the legal agreement for the development of a skyscraper building in New York. Now known as the Nordstrom Tower, when completed in 2018 it will become the world’s tallest residential building. The evaluation was carried out in two stages: original design proposal in 2005, and the final design in 2013. The background/context for the study, and the daylight injury evaluations carried out at both stages are described. The potential implications of this unique study for planning guidelines are discussed

Preventing Cholesterol-Induced Perk (Protein Kinase RNA-Like Endoplasmic Reticulum Kinase) Signaling in Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation

BACKGROUND: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling. METHODS: We generated an SMC-specific RESULTS: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 clusters of modulated SMCs in hyperlipidemic mice, one of which is absent when CONCLUSIONS: Our results indicate that hypercholesterolemia drives both Perk-dependent and Perk-independent SMC modulation and that deficiency of Perk significantly blocks atherosclerotic plaque formation

Smooth muscle hyperplasia due to loss of smooth muscle α-actin is driven by activation of focal adhesion kinase, altered p53 localization and increased levels of platelet-derived growth factor receptor-β

Mutations in ACTA2, encoding the smooth muscle cell (SMC)-specific isoform of α-actin (α-SMA), cause thoracic aortic aneurysms and dissections and occlusive vascular diseases, including early onset coronary artery disease and stroke. We have shown that occlusive arterial lesions in patients with heterozygous ACTA2 missense mutations show increased numbers of medial or neointimal SMCs. The contribution of SMC hyperplasia to these vascular diseases and the pathways responsible for linking disruption of α-SMA filaments to hyperplasia are unknown. Here, we show that the loss of Acta2 in mice recapitulates the SMC hyperplasia observed in ACTA2 mutant SMCs and determine the cellular pathways responsible for SMC hyperplasia. Acta2−/− mice showed increased neointimal formation following vascular injury in vivo, and SMCs explanted from these mice demonstrated increased proliferation and migration. Loss of α-SMA induced hyperplasia through focal adhesion (FA) rearrangement, FA kinase activation, re-localization of p53 from the nucleus to the cytoplasm and increased expression and ligand-independent activation of platelet-derived growth factor receptor beta (Pdgfr-β). Disruption of α-SMA in wild-type SMCs also induced similar cellular changes. Imatinib mesylate inhibited Pdgfr-β activation and Acta2−/− SMC proliferation in vitro and neointimal formation with vascular injury in vivo. Loss of α-SMA leads to SMC hyperplasia in vivo and in vitro through a mechanism involving FAK, p53 and Pdgfr-β, supporting the hypothesis that SMC hyperplasia contributes to occlusive lesions in patients with ACTA2 missense mutation

The Politics of Race and Class and the Changing Spatial Fortunes of the McCarren Pool in Brooklyn, New York, 1936-2010

This paper explores the changing spatial properties of the McCarren Pool and connects them to the politics of race and class. The pool was a large liberal government project that sought to improve the leisure time of working class Brooklynites and between 1936 and the early 1970s it was a quasi-public functional space. In the 1970s and the early 1980s, the pool became a quasi-public dysfunctional space because the city government reduced its maintenance and staffing levels. Working class whites of the area engaged into neighborhood defense in order to prevent the influx of Latinos and African Americans into parts of Williamsburg and Greenpoint and this included the environs of the McCarren Pool. The pool was shut down in 1983 because of a mechanical failure. Its restoration did not take place because residents and storekeepers near the vicinity of the pool complained that by the 1970s, it was only African Americans and Latinos who patronized the pool and that their presence in the neighborhood undermined white exclusivity. For two decades, the McCarren Pool became a multi-use alternative space frequented by homeless people, graffiti artists, heroin users, teenagers, and drug dealers. Unlike previous decades, during this period, people of various racial and ethnic backgrounds frequented the pool area in a relatively harmonious manner. In the early part of the twenty-first century, a neoliberal city administration allowed a corporation to organize music concerts in the pool premises and promised to restore the facility into an operable swimming pool. The problem with this restoration project is that the history of the pool between the early 1970s and the early 2000s is downplayed and this does not serve well former or future users of the poo

Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections

Chromosomal deletions or reciprocal duplications of the 16p13.1 region have been implicated in a variety of neuropsychiatric disorders such as autism, schizophrenia, epilepsies, and attention-deficit hyperactivity disorder (ADHD). In this study, we investigated the association of recurrent genomic copy number variants (CNVs) with thoracic aortic aneurysms and dissections (TAAD). By using SNP arrays to screen and comparative genomic hybridization microarrays to validate, we identified 16p13.1 duplications in 8 out of 765 patients of European descent with adult-onset TAAD compared with 4 of 4,569 controls matched for ethnicity (P = 5.0×10−5, OR = 12.2). The findings were replicated in an independent cohort of 467 patients of European descent with TAAD (P = 0.005, OR = 14.7). Patients with 16p13.1 duplications were more likely to harbor a second rare CNV (P = 0.012) and to present with aortic dissections (P = 0.010) than patients without duplications. Duplications of 16p13.1 were identified in 2 of 130 patients with familial TAAD, but the duplications did not segregate with TAAD in the families. MYH11, a gene known to predispose to TAAD, lies in the duplicated region of 16p13.1, and increased MYH11 expression was found in aortic tissues from TAAD patients with 16p13.1 duplications compared with control aortas. These data suggest chromosome 16p13.1 duplications confer a risk for TAAD in addition to the established risk for neuropsychiatric disorders. It also indicates that recurrent CNVs may predispose to disorders involving more than one organ system, an observation critical to the understanding of the role of recurrent CNVs in human disease and a finding that may be common to other recurrent CNVs involving multiple genes

Beyond the Adversial: Conflict Resolution, Simulation and Community Design

Fundamentally, the design of communities in the United States is grounded in the Constitutionis evolving definition of property and the rights and obligations attendant to the ownership and use of real property. The rearticulation of Jeffersonis dictum in the Declaration of Independence, “that individuals have certain inalienable rights, among these are life, liberty, and the pursuit of happiness” to the Constitutionis “life, liberty and property” represents a pragmatic understanding of the relationship between property and the actualization of the individual in society. In terms of community design, this means extensive public involvement and participation in not only the formulation of rules and regulations but of individual projects as well.  Since the 1960's as planning and community design decision making has become increasingly contentious, the American legal systemis adversial approach to conflict resolution has become the dominant model for public decision making. The legal systemis adversial approach to adjudication is essentially a zero-sum game of winners and losers, and as most land-use lawyers will agree, is not a good model for the design of cities. While the adversial approach does not resolve disputes it rarely creates a positive and constructive consensus for change. Because physical planning and community design issues are not only value based, community design through consensus building has emerged as a new paradigm for physical planning and design. The Environmental Simulation Center employs a broad range of complementary simulation and visualization techniques including 3-D vector based computer models, endoscopy, and verifiable digital photomontages to provide objective and verifiable information for projects and regulations under study.  In this context, a number of recent projects will be discussed which have explored the use of various simulation and visualization techniques in community design. Among them are projects involved with changes in the Cityis Zoning Regulations, the community design of a major public open space in one of the regionis mid-size cities, and the design of a new village center for a suburban community, with the last project employing the Centeris userfriendly and interactive 3-D computer kit of parts. The kit - a kind of computer “pattern booki is comprised of site planning, urban and landscape design and architectural conventions - is part of the Centeris continuing effort to support a consensus based, rather than adversial based, public planning and design process