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UK planning policies clearly state that well-designed places support the creation of sustainable places that generate positive economic, environment and social outcomes. Yet, for decades, the design value of 'new build' housing development has remained stubbornly low. Using data from a multiple case study of new housing developments across the UK's four nations, this paper asks why this persists and explores how it might be overcome. It models nine key stages in the planning, design and development process for new housing illustrating where the 'critical points of design governance intervention' lie. [ABSTRACT FROM AUTHOR]

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As consumer habits evolve the role of purpose-built shopping centers is being severely tested. The phrase “dead mall syndrome” is now frequently used in North America and parts of Europe to describe shopping centers facing obsolescence. In this paper, we make purpose-built shopping centers in large UK cities our focus and consider the extent to which “dead mall syndrome” and “de-malling” are occurring on the UK’s city center high streets. Using a new dataset, we find that shopping centers are facing high levels of vacancy and can no longer rely on the rental income that used to flow from retailers. Tenancies are also more difficult to sustain in older enclosed shopping centers than in newer open-air shopping centers. This has forced some operators to adopt radical “de-malling” measures that focus on the redevelopment of former shopping center sites into mixed-use urban quarters. This approach has been aided by flexible UK planning policies that enable shop owners to convert redundant retail space into alternative new uses. We argue, however, that a more managed approach is necessary to ensure these urban transformations achieve a sustainable fix to the “crisis on the high street” in large UK city centers. [ABSTRACT FROM AUTHOR]

Since the 1990s the UK's city centre high streets have been losing market share to out-of-town shopping and e-retailing. The shocks of the Global Financial Crisis and COVID-19 have hastened this and precipitated widespread store closures. The experience economy is increasingly promoted as a means to avert the 'death of the high street', and this prompts our study of its evolution. An exploration of the literature reveals the experience economy to be an interconnected phenomenon focused on the creation of a memorable event that elicits a sensory response via multi-dimensional innovation and design. Using this to guide our empirical work, we undertake a comparative mixed method longitudinal case study of five UK city centres. We initially chart the changing manifestations of experience uses before analysing supporting interviews and observations that reveal three interconnected layers of the experience economy: in-store commercial experiences; leisure and entertainment-orientated adaptations to shopping centres and department stores; and the wider regeneration of the public realm. Implications for city centre management are discussed. [ABSTRACT FROM AUTHOR]

In this paper, the density and location of retail properties located within the primary retailing areas of Edinburgh, Glasgow, Hull, Liverpool and Nottingham are investigated over a 17 year period. The study is novel due to the original spatial databases developed and unique combination of established methods employed to explore spatial change within these northern UK cities. The paper starts from the premise that retailing markets display adaptive resilience where adaptations in use and variation in retail clustering will occur in response to endogenous and exogenous shocks that disturb the market's agglomerative and competitive effects. The results suggest that significant new retail-led developments have intra-urban spatial outcomes that impact on the size and location of prime and secondary retailing pitches. In urban retailing centres where there have been no substantive supply disruptions, disturbances in the socio-economic environment can create contractions at the peripheral edges of the prime retailing pitch. This study is significant in providing a historical perspective of the micro-level effects of new development, changing customer shopping habits and shifting retailer location preferences. In addition, the research develops replicable and robust methods that can be employed to examine and monitor spatial change in urban centres. Understanding these dynamic micro-spatial effects are important for the future management of urban centres. [ABSTRACT FROM AUTHOR]

The retailing industry in the UK is experiencing unprecedented structural change. The impact on retailers has often dominated headlines, along with the impacts on local services and economies, but with little attention given to the implications for property owners and practitioners. Exploring and understanding the responsiveness of landlords, and their behaviours, is essential to understanding the adaptiveness of a retailing system. This study employs semi-structured interviews to examine the short- and long-term changes in the retail market and the actions of landlords in response. The findings span the period prior to and during the first year of the Covid-19 pandemic in 2020, and reveal that fundamental changes have occurred to establish tenant covenant norms and the traditional retail leasing model. The paper explores these changes, including a shift in tenant risk, reposition of the leasing model in favour of tenants, generally, and greater application of turnover rents. The pressing challenge for current valuation practitioners, therefore, is to incorporate these fundamental changes within the market into the pricing of retail assets. Significant progress in this area to date, as explored in the paper, has been limited although greater application of discounted cashflow techniques is set to be encouraged by the RICS. [ABSTRACT FROM AUTHOR]

This paper considers how planning authorities can achieve urban design ambitions in the context of deepening neoliberalism and fiscal austerity. Based upon a case study of West Dunbartonshire, Scotland, the paper reveals the innovative steps taken by the local authority to introduce new design governance tools in the face of significant resource constraints. The paper critically examines the role that the private sector plays in the governance of design and argues for a reconceptualisation of design governance that more rigorously attends to the challenge of delivering well-designed places in the public interest. [ABSTRACT FROM AUTHOR]

Brown, Peter Hendee. America's Waterfront Revival: Port Authorities and Urban Redevelopment. Philadelphia: University of Pennsylvania Press, 2009. 228 pp. ISBN: 9780812241228. Many authors have explored the local and global implications [...]

This paper investigates the formal instruments of design governance and the urban design decision-making environment in Chinese cities. It identifies Shenzhen, Shanghai and Nanjing as three cities pioneering in design-led planning in China and critically evaluates their approaches using a series of 'best practice' principles for design review and development management. The findings are based on 20 semi-structured interviews with key stakeholders, a review of their design portfolios, and an analysis of urban design policies and plans. The paper identifies the progress made with design governance in the three 'pioneer' cities as well as the challenges associated with adopting more design-sensitive planning practice. It concludes with four recommendations for Chinese cities. These focus on foregrounding sense of place in city-wide urban design visions, raising the quality of design guidance and codes, more effectively coordinating regulations produced by different government departments and agencies, and widening opportunities for public participation. [ABSTRACT FROM AUTHOR]

This practice paper reflects on the national design advice service in Scotland that has been operated by Architecture & Design Scotland (A&DS) since 2005. Placed in the context of research on design review practice, the paper describes how design review in Scotland has evolved from a traditional panel model operating alongside a range of training and skills development functions into a more holistic and dynamic design advice service. The paper argues that the evolution of design review in Scotland signifies an innovative shift away from the often combative setting of a design panel, where the force of an argument frequently wins the day, towards a more measured, iterative and collaborative process of nurturing and enabling well-designed buildings and places. [ABSTRACT FROM AUTHOR]

This paper reassesses John Punter's ‘Best Practice Principles for Design Review and Development Management’ that were published in this journal in 2007. Placing a focused lens on British and North American practice, the paper argues that design control and review has been profoundly reshaped since 2007 by three contributing factors: the challenges associated with climate change, the growing role that communities can play in local decision making, and the impacts of the global economic crisis upon public sector finances and property development. In light of these trends, the paper uses a review of recent literature and design practices to argue for a series of amendments to the best practice principles. These focus on: (1) the potential for design control and review to be more fully informed by ecological design theory and practice; (2) the need for more rigorous multi-stakeholder collaboration in the design decision-making process; and (3) the opportunity for urban designers to become more competent ‘market actors’ with the necessary abilities to confidently shape property development decisions. [ABSTRACT FROM PUBLISHER]

Design competitions are often used to select design teams for high profile development projects, yet have received scant attention in the literature. Seeking to redress this imbalance, this paper presents a competition model that was employed on Toronto’s waterfront in 2006 for a large public realm project and describes how it was structured around an iterative public consultation process. Although subject to a number of implementation delays, the competition sponsors built a constituency of support for the redevelopment project by engaging lay people in the decision-making process. The paper argues that the competition struck a balance between lay input and professional knowledge and contends that future research efforts should continue to explore means by which public participation can be integrated into design competitions. [ABSTRACT FROM PUBLISHER]

Androgens regulate important processes involved in the normal development and function of the human and rodent prostate glands. Here we report the isolation and characterization of a new androgen-regulated gene, designated WDR19, that encodes repeating sequence motifs found in the WD-repeat family of proteins. The WD repeat is a conserved domain of approximately 40 amino acids that is typically bracketed by glycine–histidine and tryptophan–aspartic acid (WD) dipeptides. WD-repeat proteins are a large group of structurally related proteins that participate in a wide range of cellular functions, including transmembrane signaling, mRNA modification, vesicle formation, and vesicular trafficking. The WDR19 gene comprises 36 exons and is located on chromosome 4p15–4p11. The predicted protein contains six WD repeats, a clathrin heavy-chain repeat, and three transmembrane domains. Sequence analysis reveals that the WDR19 gene is conserved from Caenorhabditis elegans to human. WDR19 is expressed in normal and neoplastic prostate epithelium as demonstrated by RNA in situ hybridization and is regulated by androgenic hormones. WDR19 transcripts exhibit alternative splicing in which two isoforms appear to be prostate restricted, a property that could be exploited for designing diagnostic or therapeutic strategies for prostate carcinoma. [Copyright &y& Elsevier]

Design students are increasingly seeking precedent information through web-based digital archives of design cases. Little is known, however, about the use, relative merits or opportunities of digital cases as a knowledge source for design students. This paper uses a study of web-based urban design reference tools to examine new opportunities for using precedents in urban design. The research includes focus groups, content analysis of student work and an auto-ethnography by one of the authors to examine student use of the reference tools in 3 urban design studios in planning and landscape architecture. Students used 3-D digital models of precedents to review, replicate, revise, reshape and recreate elements of urban design in an environment of accelerated learning. [Copyright &y& Elsevier]

Chemotherapy with carboplatin and paclitaxel is the standard treatment for ovarian cancer patients. Although most patients initially respond to this treatment, few are cured. Resistance to chemotherapy is the major cause of treatment failure. We applied a quantitative proteomic approach based on ICAT/MS/MS technology to analyze tissues harvested at primary debulking surgery before the initiation of combination chemotherapy in order to identify potential naive or intrinsic chemotherapy response proteins in ovarian cancers. We identified 44 proteins that are overexpressed, and 34 proteins that are underexpressed in the chemosensitive tissue compared to the chemoresistant tissue. The overexpressed proteins identified in the chemoresistant tissue include 10 proteins (25.6%) belonging to the extracellular matrix (ECM), including decorin, versican, basigin (CD147), fibulin-1, extracellular matrix protein 1, biglycan, fibronectin 1, dermatopontin, alpha-cardiac actin (smooth muscle actin), and an EGF-containing fibulin-like extracellular matrix protein 1. Interesting proteins identified as overexpressed in the chemosensitive tissue include gamma-catenin (junction plakoglobin) and delta-catenin, tumor suppressor p53-binding protein 1 (53BP1), insulin-like growth factor-binding protein 2 (IGFBP2), proliferating cell nuclear antigen (PCNA), annexin A11, and 53 kDa selenium binding protein 1. Integrative analysis with expression profiling data of eight chemoresistant tissues and 13 chemosensitive tissues revealed that 16 proteins showed consistent changes at both the protein and the RNA levels. These include P53 binding protein 1, catenin delta 1 and plakoglobin, EGF-containing fibulin-like extracellular matrix protein 1 and voltage-dependent anion-selective channel protein 1. Our results suggest that chemotherapy response may be determined by multiple and complex system properties involving extracellular-matrix, cell adhesion and junction proteins.

Epithelial ovarian cancer (EOC) ranks fifth as a cause of cancer deaths in women. Current diagnostic and monitoring markers have limited reliability for the detection of disease. We have tested the possibility of identifying candidate biomarkers present at low nanogram to picogram levels after removing both the 12 most abundant and 77 moderately abundant proteins from serum samples of EOC patients using antibody affinity columns. We showed that this approach allows the identification of proteins that are expressed at nanogram per liter levels in the serum. Using ICAT/MS/MS analysis, we identified 51 proteins that are differentially expressed by at least twofold. These proteins include leucine-rich alpha-2-glycoprotein, matrix metalloproteinase-9 (MMP-9), inter-alpha-trypsin inhibitor heavy chain H1, insulin-like growth factor-binding protein 6, insulin-like growth factor-binding protein 3, isoform 1 of epidermal growth factor receptor, angiopoietin-like protein 3 (ANGPTL3) and phosphatidylcholine-sterol acyltransferase. We confirmed the differential expression of MMP9 and ANGPTL3 in normal and ovarian cancer sera by ELISA assays. Further robust clinical evaluation of the candidate markers identified is necessary.

Purpose: Prostate cancer is the third leading cause of cancer death in the United States, following lung and colorectal cancer. We previously identified WDR19 as a prostate-specific, androgen-regulated gene. Here, we evaluate its utility as a prostate cancer tissue marker for diagnosis and prognostic evaluation., Experimental Design: Real-time quantitative PCR was done on a panel of prostate tissue isolated by laser capture microdissection. After generating antibodies against WDR19, tissue microarrays (TMA) were employed to compare WDR19 expression between normal, benign prostatic hyperplasia, and prostate cancer tissue., Results: Using microarrays and real-time quantitative PCR, we showed that WDR19 mRNA expression was increased in cancer. We further showed that WDR19 protein is localized to cytoplasmic subcellular granules and is expressed exclusively in prostate epithelia. Large-scale immunohistochemical staining using TMAs reveals a significant percentage of increase in intensely staining tissue cores in cancer tissue when compared with normal or benign prostatic hyperplastic tissue. Based on the analysis of a separate TMA for which clinical follow-up information was available, low-intensity WDR19 staining was significantly associated with decreased time to biochemical failure (P = 0.006) and with decreased time to locoregional recurrence (P = 0.050)., Conclusions: WDR19 should be added to the list of prostate cancer tissue markers. The continued expansion of a multiple-marker panel will conceivably increase the sensitivity and specificity of prostate cancer diagnosis and prognosis.

We present a robust and general shotgun glycoproteomics approach to comprehensively profile glycoproteins in complex biological mixtures. In this approach, glycopeptides derived from glycoproteins are enriched by selective capture onto a solid support using hydrazide chemistry followed by enzymatic release of the peptides and subsequent analysis by tandem mass spectrometry. The approach was validated using standard protein mixtures that resulted in a close to 100% capture efficiency. Our capture approach was then applied to microsomal fractions of the cisplatin-resistant ovarian cancer cell line IGROV-1/CP. With a Protein Prophet probability value greater than 0.9, we identified a total of 302 proteins with an average protein identification rate of 136 +/- 19 (n = 4) in a single linear quadrupole ion trap (LTQ) mass spectrometer nano-LC-MS experiment and a selectivity of 91 +/- 1.6% (n = 4) for the N-linked glycoconsensus sequence. Our method has several advantages. 1) Digestion of proteins initially into peptides improves the solubility of large membrane proteins and exposes all of the glycosylation sites to ensure equal accessibility to capture reagents. 2) Capturing glycosylated peptides can effectively reduce sample complexity and at the same time increase the confidence of MS-based protein identifications (more potential peptide identifications per protein). 3) The utility of sodium sulfite as a quencher in our capture approach to replace the solid phase extraction step in an earlier glycoprotein chemical capture approach for removing excess sodium periodate allows the overall capture procedure to be completed in a single vessel. This improvement minimizes sample loss, increases sensitivity, and makes our protocol amenable for high throughput implementation, a feature that is essential for biomarker identification and validation of a large number of clinical samples. 4) The approach is demonstrated here on the analysis of N-linked glycopeptides; however, it can be applied equally well to O-glycoprotein analysis.

Nearly all women diagnosed with ovarian cancer receive combination chemotherapy including cis- or carboplatin. Despite high initial response rates, resistance to cisplatin develops in roughly one-third of women during primary treatment and in all women treated for recurrent disease. ICAT coupled with tandem MS is a quantitative proteomic technique for high throughput protein expression profiling of complex protein mixtures. Using ICAT/MS/MS we profiled the nuclear, cytosolic, and microsomal fractions obtained from IGROV-1 [corrected] (cisplatin-sensitive) and IGROV-1/CP [corrected] (cisplatin-resistant) ovarian cancer cell lines. The proteomes of cisplatin-sensitive and -resistant ovarian cancer cells were compared, and protein expression was correlated with mRNA expression profiles. A total of 1117 proteins were identified and quantified. The relative expression of 121 of these varied between the two cell lines. Sixty-three proteins were overexpressed in cisplatin-sensitive, and 58 were over expressed in cisplatin-resistant cells. Examples of proteins at least 5-fold overexpressed in resistant cells and with biological relevance to cancer include cell recognition molecule CASPR3 (13.3-fold), S100 protein family members (8.7-fold), junction adhesion molecule Claudin 4 (7.2-fold), and CDC42-binding protein kinase beta (5.4-fold). Examples of cancer-related proteins at least 5-fold overexpressed in sensitive cells include hepatocyte growth factor inhibitor 1B (13.3-fold) and programmed cell death 6-interacting protein (12.7-fold). The direction of changes in expression levels between proteins and mRNAs were not always in the same direction, possibly reflecting posttranscriptional control of protein expression. We identified proteins whose expression profiles correlate with cisplatin resistance in ovarian cancer cells. Several proteins may be involved in modulating response to cisplatin and have potential as markers of treatment response or treatment targets.

Prostate cancer is initially responsive to androgen ablation therapy and progresses to androgen-unresponsive states that are refractory to treatment. The mechanism of this transition is unknown. A systems approach to disease begins with the quantitative delineation of the informational elements (mRNAs and proteins) in various disease states. We employed two recently developed high-throughput technologies, massively parallel signature sequencing (MPSS) and isotope-coded affinity tag, to gain a comprehensive picture of the changes in mRNA levels and more restricted analysis of protein levels, respectively, during the transition from androgen-dependent LNCaP (model for early-stage prostate cancer) to androgen-independent CL1 cells (model for late-stage prostate cancer). We sequenced >5 million MPSS signatures, obtained >142,000 tandem mass spectra, and built comprehensive MPSS and proteomic databases. The integrated mRNA and protein expression data revealed underlying functional differences between androgen-dependent and androgen-independent prostate cancer cells. The high sensitivity of MPSS enabled us to identify virtually all of the expressed transcripts and to quantify the changes in gene expression between these two cell states, including functionally important low-abundance mRNAs, such as those encoding transcription factors and signal transduction molecules. These data enable us to map the differences onto extant physiologic networks, creating perturbation networks that reflect prostate cancer progression. We found 37 BioCarta and 14 Kyoto Encyclopedia of Genes and Genomes pathways that are up-regulated and 23 BioCarta and 22 Kyoto Encyclopedia of Genes and Genomes pathways that are down-regulated in LNCaP cells versus CL1 cells. Our efforts represent a significant step toward a systems approach to understanding prostate cancer progression.

Background: Prostasomes are secretory particles in human seminal fluid. Other than a microscopic description of these secretory particles and an incomplete two-dimensional gel electrophoresis (2DE) study, little is known about the composition of proteins in prostasomes., Methods: We employed a direct iterative approach using Gas phase fractionation and microcapillary HPLC-tandem mass spectrometry (microLC-MS/MS) to catalogue the prostasome proteome., Results: We identified 139 proteins that can be divided into the following categories: (1). enzymes (33.8% of total), (2). transport/structural (19.4% of total), (3). GTP proteins (14.4% of total), (4). chaperone proteins (5.8% of total), (5). signal transduction proteins (17.3% of total), and (6). unannotated proteins (9.4% of total). A total of 128 of the 139 proteins have not previously been described as prostasomal., Conclusions: The proteins identified can be used as reference dataset in future work comparing prostasome proteins between normal and pathological states such as prostate cancer, benign prostatic hyperplasia, prostatitis, and infertility., (Copyright 2003 Wiley-Liss, Inc.)