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Comparing case studies of long-term, large-scale urban regeneration projects in Glasgow and Edinburgh, Scotland, this paper brings together two addendums to the rent gap model in the shape of the ‘reputational gap’ and the ‘state subsidy gap’. These neologisms are mobilised to clarify the risk-laden centrality of the state’s role in both the formation and potential closure of rent gaps in large-scale areas of disinvestment and devalorisation. Whilst such projects often appear as expressions of capital’s state-mediated extractive power over the built environment, we consider them as examples of capitalist failure or fragility – for even with striking levels of public subsidy to address ‘market failure’ the land and property market has not been reinvigorated according to plan. This highlights the need, we argue, for further critical scrutiny of failed or stalled urban regeneration projects as a means of foregrounding the instability, rather than the omnipotence, of contemporary urban capitalism.

Autonomist Marxist ideas and concepts are resurgent and, with their latent spatiality, are well placed to contribute to radical geographical debates. In particular, the methodology of ‘class composition’ analysis provides a rigorous, materialist critique of transforming capitalist social relations. This paper first provides vital historical–theoretical context from the milieu of Italian Operaismo, before emphasising the value of autonomist Marxist analyses of three contemporary geographical frontiers: labour process, migration, and social reproduction. It ultimately argues that the laudable motivations of the autonomous geographies project, explored in this very journal, would be better served through an explicitly materialist autonomist geography.

Supplementary Tables S1-S2.

PDF file - 78K, Mutation status of AZ samples acquired through Liverpool Heart and Chest Hospital.

PDF file - 129K, Reduced nuclear PTEN in SCC compared with AC (TMA Set 2).

PDF file - 145K, Isoform specificity of PI3Kbeta antibody (AGG4888).

PDF file - 57K, Clinicopathological features of TMA Set 1.

PDF file - 221K, Validation of PTEN antibody across FFPE xenograft samples.

Purpose: Vascular endothelial growth factor (VEGF) signaling is key to tumor angiogenesis and is an important target in the development of anticancer drugs. However, VEGF receptor (VEGFR) expression in human cancers, particularly the relative expression of VEGFR-2 and VEGFR-3 in tumor vasculature versus tumor cells, is poorly defined.Experimental Design: VEGFR-2– and VEGFR-3–specific antibodies were identified and used in the immunohistochemical analysis of human primary cancers and normal tissue. The relative vascular localization of both receptors in colorectal and breast cancers was determined by coimmunofluorescence with vascular markers.Results: VEGFR-2 and VEGFR-3 were expressed on vascular endothelium but not on malignant cells in 13 common human solid tumor types (n > 400, bladder, breast, colorectal, head and neck, liver, lung, skin, ovarian, pancreatic, prostate, renal, stomach, and thyroid). The signal intensity of both receptors was significantly greater in vessels associated with malignant colorectal, lung, and breast than adjacent nontumor tissue. In colorectal cancers, VEGFR-2 was expressed on both intratumoral blood and lymphatic vessels, whereas VEGFR-3 was found predominantly on lymphatic vessels. In breast cancers, both receptors were localized to and upregulated on blood vessels.Conclusions: VEGFR-2 and VEGFR-3 are primarily localized to, and significantly upregulated on, tumor vasculature (blood and/or lymphatic) supporting the majority of solid cancers. The primary clinical mechanism of action of VEGF signaling inhibitors is likely to be through the targeting of tumor vessels rather than tumor cells. The upregulation of VEGFR-3 on tumor blood vessels indicates a potential additional antiangiogenic effect for dual VEGFR-2/VEGFR-3–targeted therapy. Clin Cancer Res; 16(14); 3548–61. ©2010 AACR.

Purpose: The phosphoinositide 3-kinase (PI3K) pathway is a major oncogenic signaling pathway and an attractive target for therapeutic intervention. Signaling through the PI3K pathway is moderated by the tumor suppressor PTEN, which is deficient or mutated in many human cancers. Molecular characterization of the PI3K signaling network has not been well defined in lung cancer; in particular, the role of PI3Kβ and its relation to PTEN in non–small cell lung cancer NSCLC remain unclear.Experimental Design: Antibodies directed against PI3Kβ and PTEN were validated and used to examine, by immunohistochemistry, expression in 240 NSCLC resection tissues [tissue microarray (TMA) set 1]. Preliminary observations were extended to an independent set of tissues (TMA set 2) comprising 820 NSCLC patient samples analyzed in a separate laboratory applying the same validated antibodies and staining protocols. The staining intensities for PI3Kβ and PTEN were explored and colocalization of these markers in individual tumor cores were correlated.Results: PI3Kβ expression was elevated significantly in squamous cell carcinomas (SCC) compared with adenocarcinomas. In contrast, PTEN loss was greater in SCC than in adenocarcinoma. Detailed correlative analyses of individual patient samples revealed a significantly greater proportion of SCC in TMA set 1 with higher PI3Kβ and lower PTEN expression when compared with adenocarcinoma. These findings were reinforced following independent analyses of TMA set 2.Conclusions: We identify for the first time a subset of NSCLC more prevalent in SCC, with elevated expression of PI3Kβ accompanied by a reduction/loss of PTEN, for whom selective PI3Kβ inhibitors may be predicted to achieve greater clinical benefit. Clin Cancer Res; 20(3); 595–603. ©2013 AACR.

PDF file - 133K,Reduced nuclear PTEN in SCC compared with AC (TMA Set 1).

PDF file - 61K, Clinicopathological features of TMA Set 2.

CRISPR-Cas systems comprise diverse adaptive immune systems in prokaryotes whose RNA-directed nucleases have been co-opted for various technologies. Recent efforts have focused on expanding the number of known CRISPR-Cas subtypes to identify nucleases with novel properties. However, the functional diversity of nucleases within each subtype remains poorly explored. Here, we used cell-free transcription-translation systems and human cells to characterize six Cas12a single-effector nucleases from the V-A subtype, including nucleases sharing high sequence identity. While these nucleases readily utilized each other's guide RNAs, they exhibited distinct PAM profiles and apparent targeting activities that did not track based on phylogeny. In particular, two Cas12a nucleases encoded by Prevotella ihumii (PiCas12a) and Prevotella disiens (PdCas12a) shared over 95% amino-acid identity yet recognized distinct PAM profiles, with PiCas12a but not PdCas12a accommodating multiple G’s in PAM positions -2 through -4 and T in position -1. Mutational analyses transitioning PiCas12a to PdCas12a resulted in PAM profiles distinct from either nuclease, allowing more flexible editing in human cells. Cas12a nucleases therefore can exhibit widely varying properties between otherwise related orthologs, suggesting selective pressure to diversify PAM recognition and supporting expansion of the CRISPR toolbox through ortholog mining and PAM engineering.

MX80 bentonite has been selected as the buffer and backfill in a proposed method of long-term deep geological storage of nuclear waste. Extensive studies have been carried out on the geomechanical properties of MX80; however, it is not clear what effect microbes will have on its ability to function as an effective barrier. Specifically, in the UK, as carbon steel waste canisters will contribute iron oxides and rust products to the immediate environment, iron-reducing bacteria are of interest. Iron-reducing bacteria can reduce structural or external Fe (III) to Fe (II) and some species are adapted to high temperatures and low water availability, in keeping with conditions within the waste repository. Indigenous iron-interacting bacteria have been identified in compacted MX80 and microbially-influenced iron-reduction was observed in groundwater salinity up to 0.45M NaCl. Experiments investigating gas production, and silica-solubilising abilities of this community were carried out. Further experiments in pressurised test cells investigated microbial activities at the clay / steel interface. Significant increases in hydrogen production were observed when microbes were present, and biogenically influenced changes in structure and appearance of MX80 were seen in all experiments. Additionally, silica release occurred, likely coupled to metal / microbe interactions. Corrosion products differed depending on microbial presence following incubation in test cells. Biogenic transformation of clay minerals through iron reduction or release of silica to groundwater could significantly impact the geomechanical properties of MX80, as indicated by observed changes in clay plasticity, and ultimately this could affect the behavior of the material as a barrier.

Class composition was the most important concept to be developed within the rich milieu of Italian autonomist Marxism, acutely addressing subject-object dichotomies and organisational problems of internal differentiation in and between classed, raced and gendered social formations. Yet “compositionist” analysis has received remarkably little attention within urban-geographical literatures. This paper reviews and develops the class composition concept, offering the first fully developed theorisation of spatial composition and underscoring its relevance for a contemporary politics of space. It stresses the importance of immanent, reflexive non-teleological periodisations of capitalist relations for anti-capitalist struggle through the intertwined concepts of spatial composition and the tendency. Through this theoretical lens it narrates the innovative and under-examined spatial praxis of often women-led urban movements in 1970s Italy, arguing that these remarkable struggles provide vital lessons for thinking through the diverse modalities of organisation and class recomposition emerging in the material geographies of social reproduction today.

Safe as Houses: Private Greed, Political Negligence and Housing Policy After Grenfell Stuart Hodkinson, Safe as Houses: Private Greed, Political Negligence and Housing Policy After Grenfell, Manchester: Manchester University Press, 2019; 272 pp.: 978-1-5261-2998-7, £11.99 (pbk).

Over the last decennia, alkaline leachates from the weathering of legacy steel slag disposal sites have affected the surrounding soils and drainage streams. The hyperalkaline and hypersaline conditions around these sites are comparable to extreme paleo environments such as alkaline lakes in rift volcanic settings. Investigating the carbonate deposits forming in these man-made systems provides a unique opportunity to link the ongoing physical and microbial processes to their resultant carbonate morphologies.Here we present data from 3 sites across Dene Burn, a slag drainage stream in Consett, County Durham, UK. After 100 years, iron and steel production ceased in 1980, leaving over 20 million tons of slag in the form of several large mounds. Analysis showed Dene Burn to be typical of slag drainage waters with an elevated pH (>9) and saturated with different secondary phase minerals- particularly calcite. However, the physical distribution of carbonates is more comparable with estimated local kinetic precipitation rate than it is to thermodynamic saturation, indicating that the fundamental control on carbonate formation arises from crystal surface processes. A microbial community comprising predominantly Proteobacteria (Alpha-, Gamma-, Beta- and Deltaproteobacteria), Cyanobacteria, Bacillariophyta (diatoms) and Bacteroidetes (Flavobacterium) was identified at the 3 sites. The microbial communities and an abundance of extracellular polymeric substances (EPS) were shown in close association with the mineral phases detected at the sites. The presence and composition of these biofilms appears to control local carbonate mineralisation rates and carbonate morphologies.Drainage streams from steel slag provide a unique opportunity to study carbonate mineral formation under extreme environmental conditions. Furthermore, maximising carbonate formation at such sites could be utilised as a remediation and carbonate sequestration technique.

After breaking ground back in 2011, Disney and Shanghai Shendi Group officially opened the spectacular new Shanghai Disneyland resort on 16th June 2016. This latest resort in China has six themed lands including ‘Tomorrowland’ featuring popular futuristic Disney characters including Tron, Lilo and Stich, and Toy Story's Buzz Lightyear. Extensive sections of both the interior and exterior of the buildings and show-sets in Tomorrowland, covering a total area of over 2300 m2, were constructed from fire retardant (FR) gelcoated composite molded parts in several hundred different complex shaped and sized components.

The new digital banking group BBVA headquarters building in Madrid, designed by architecture firm Herzog & de Meuron, is kept cooler using sandwich laminate design composite sun panels which form an integral part of the contemporary new building facade. Summer temperatures in Madrid can reach over 30°C by midday, so having environmentally friendly ways to minimize air-conditioning energy usage inside its new head office was high on the agenda for BBVA, given its strong commitment to using renewable energy and buildings with the highest environmental certification. The use of innovative composite sun panels in front of the glass windows around the new BBVA building achieved this energy saving corporate objective in grand style.

The new enclosure: The appropriation of public land in Neoliberal Britain, by Brett Christophers, Verso, London, 2019, xviii + 362 pp., £20.00 (hbk), ISBN-13: 978-1-78663-158-9, https://www.versobooks.com/books/2871-the-new-enclosure.

This chapter takes up a critical discussion of the celebrated right to the city thesis to examine the significant constraints that can emerge from a rights-based approach. The chapter explores a property conflict ignited by the 2014 Glasgow Commonwealth Games and its related urban renewal projects, in which the state used a Compulsory Purchase Order, a kind of emergency measure for property, to evict one family. Alongside a critical stance on the political implications and possibilities of invoking the right to the city, the chapter seeks to go beyond rights and recognition claims by combining a relational view of property and space with an empirical narration of one familys struggle to keep their property while confronting a state determined to evict them.

CRISPR-based genome editing is an enabling technology with potential to dramatically transform multiple industries. Identification of additional editing tools will be imperative for broad adoption and application of this technology. A novel Type V, Class 2 CRISPR nuclease system was identified from Microgenomates and Smithella bacterial species (CRISPR from Microgenomates and Smithella, Cms1). This system was shown to efficiently generate indel mutations in the major crop plant rice (Oryza sativa). Cms1 are distinct from other Type V nucleases, are smaller than most other CRISPR nucleases, do not require a tracrRNA, and have an AT-rich protospacer-adjacent motif site requirement. A total of four novel Cms1 nucleases across multiple bacterial species were shown to be functional in a eukaryotic system. This is a major expansion of the Type V CRISPR effector protein toolbox and increases the diversity of options available to researchers.

When compulsory purchase for urban regeneration is combined with a sporting mega-event, we have an archetypal example of what Giorgio Agamben called the "state of exception". Through a study of compulsory purchase orders (CPOs) on the site of the Athletes' Village for Glasgow's 2014 Commonwealth Games, we expose CPOs as a classed tool mobilised to violently displace working class neighbourhoods. In doing so, we show how a fictionalised mantra of "necessity" combines neoliberal growth logics with their obscene underside-a stigmatisation logic that demonises poor urban neighbourhoods. CPOs can be used progressively, for example to abrogate the power of slum landlords for social democratic ends, yet with the increasing urbanisation of capital they more often target marginalised neighbourhoods in the pursuit of land and property valorisation. The growing use of CPOs as an exceptional measure in urbanisation, we argue, requires urgent attention in urban political struggles and policy practice.

Purpose: The phosphoinositide 3-kinase (PI3K) pathway is a major oncogenic signaling pathway and an attractive target for therapeutic intervention. Signaling through the PI3K pathway is moderated by the tumor suppressor PTEN, which is deficient or mutated in many human cancers. Molecular characterization of the PI3K signaling network has not been well defined in lung cancer; in particular, the role of PI3Kβ and its relation to PTEN in non–small cell lung cancer NSCLC remain unclear. Experimental Design: Antibodies directed against PI3Kβ and PTEN were validated and used to examine, by immunohistochemistry, expression in 240 NSCLC resection tissues [tissue microarray (TMA) set 1]. Preliminary observations were extended to an independent set of tissues (TMA set 2) comprising 820 NSCLC patient samples analyzed in a separate laboratory applying the same validated antibodies and staining protocols. The staining intensities for PI3Kβ and PTEN were explored and colocalization of these markers in individual tumor cores were correlated. Results: PI3Kβ expression was elevated significantly in squamous cell carcinomas (SCC) compared with adenocarcinomas. In contrast, PTEN loss was greater in SCC than in adenocarcinoma. Detailed correlative analyses of individual patient samples revealed a significantly greater proportion of SCC in TMA set 1 with higher PI3Kβ and lower PTEN expression when compared with adenocarcinoma. These findings were reinforced following independent analyses of TMA set 2. Conclusions: We identify for the first time a subset of NSCLC more prevalent in SCC, with elevated expression of PI3Kβ accompanied by a reduction/loss of PTEN, for whom selective PI3Kβ inhibitors may be predicted to achieve greater clinical benefit. Clin Cancer Res; 20(3); 595–603. ©2013 AACR.

Precise genome editing of plants has the potential to reshape global agriculture through the targeted engineering of endogenous pathways or the introduction of new traits. To develop a CRISPR nuclease-based platform that would enable higher efficiencies of precise gene insertion or replacement, we screened the Cpf1 nucleases from Francisella novicida and Lachnospiraceae bacterium ND2006 for their capability to induce targeted gene insertion via homology directed repair. Both nucleases, in the presence of a guide RNA and repairing DNA template flanked by homology DNA fragments to the target site, were demonstrated to generate precise gene insertions as well as indel mutations at the target site in the rice genome. The frequency of targeted insertion for these Cpf1 nucleases, up to 8%, is higher than most other genome editing nucleases, indicative of its effective enzymatic chemistry. Further refinements and broad adoption of the Cpf1 genome editing technology have the potential to make a dramatic impact on plant biotechnology.

BRCA1 protein measurement has previously been evaluated as a potential diagnostic marker without reaching a conclusive recommendation. In this study, we applied current best practice in antibody validation to further characterize MS110, a widely used antibody targeting BRCA1. Antibody specificity was investigated using different biochemical validation techniques. We found that BRCA1 could not be reliably detected using immunoprecipitation and Western blot in endogenously expressing cells. We used immunohistochemistry on formalin-fixed paraffin-embedded cell pellets to establish compatibility with formalin-fixed paraffin-embedded samples. We demonstrated that in transfected cells and cell lines with known genetic BRCA1 status, MS110 successfully detected BRCA1 giving the expected level of staining in immunohistochemistry. Following this, we investigated the use of BRCA1 protein measurement by immunohistochemistry in a cohort of triple negative breast and serous ovarian tumour samples to explore the use of BRCA1 protein measurement by immunohistochemistry for patient stratification. Using MS110 in repeated standardized experiments, on serial sections from a panel of patient samples, results demonstrated considerable run-to-run variability. We concluded that in formalin-fixed tissue samples, MS110 does detect BRCA1; however, using standard methodologies, BRCA1 expression levels in tissue samples is incompatible with the use of this protein as a statistically robust patient selection marker in immunohistochemistry. These results demonstrate the need for further development to deliver BRCA1 protein quantification by immunohistochemistry as a patient stratification marker.

AZD8055 is a small-molecule inhibitor of mTOR (mammalian target of rapamycin) kinase activity. The present review highlights molecular and phenotypic differences between AZD8055 and allosteric inhibitors of mTOR such as rapamycin. Biomarkers, some of which are applicable to clinical studies, as well as biological effects such as autophagy, growth inhibition and cell death are compared between AZD8055 and rapamycin. Potential ways to develop rational combinations with mTOR kinase inhibitors are also discussed. Overall, AZD8055 may provide a better therapeutic strategy than rapamycin and analogues.

Focusing on Glasgow’s East End, home to the 2014 Commonwealth Games, this paper explores the ways in which narratives of decline, ‘blight’ and decay play a central role in stigmatising the local population. ‘Glasgow East’ represents the new urban frontier in a city that has been heralded in recent decades as a model of successful post‐industrial transformation. Utilising Loic Wacquant’s arguments about advanced marginality and territorial stigmatisation in the urban context, we argue that narratives of decline and redevelopment are part of a wider ideological onslaught on the local population, intended to pave the way for low grade and flexible forms of employment, for punitive workfare schemes and for upwards rent restructuring. To this end, the media and politicians have played a particularly important role in constructing Glasgow East as a marker of a ‘broken Britain’. While the focus of this paper is on Glasgow’s East End, the arguments therein have a wider UK and global resonance, reflected in the nu...

Advances in scientific understanding of disease together with introduction of new high throughput technologies have led to increased demand for human tissue in research. In general, patients are willing to donate for research, particularly samples that are surplus to diagnostic or therapeutic requirements. New tissue-specific regulations in the UK are intended to facilitate the use of human tissue in research. Despite this positive environment there are challenges to researcher access. Coordinated, systematic collection and storage, via a biobank can provide easier access. However translating a vision for a biobank into reality whether in the public or private sector, has never been simple. But it can be done.

Summary CRISPR-Cas systems offer versatile technologies for genome engineering, yet their implementation has been outpaced by ongoing discoveries of new Cas nucleases and anti-CRISPR proteins. Here, we present the use of E. coli cell-free transcription-translation (TXTL) systems to vastly improve the speed and scalability of CRISPR characterization and validation. TXTL can express active CRISPR machinery from added plasmids and linear DNA, and TXTL can output quantitative dynamics of DNA cleavage and gene repression—all without protein purification or live cells. We used TXTL to measure the dynamics of DNA cleavage and gene repression for single- and multi-effector CRISPR nucleases, predict gene repression strength in E. coli , determine the specificities of 24 diverse anti-CRISPR proteins, and develop a fast and scalable screen for protospacer-adjacent motifs that was successfully applied to five uncharacterized Cpf1 nucleases. These examples underscore how TXTL can facilitate the characterization and application of CRISPR technologies across their many uses.

Polymeric “smart” coatings have been developed that are capable of both detecting and removing hazardous nuclear and heavy metal contaminants from contaminated surfaces. These coatings consist of strippable polymeric compositions containing blends of polymers, copolymers and additives that can be brushed or sprayed onto a surface as a solution or dispersion in aqueous media. Upon drying, these coatings form strong films that can easily be peeled or stripped from the surface. When applied to a contaminated surface, these coatings display responsive behavior. Areas of contamination are indicated by a color change. As the coatings dry, the contaminants are drawn into and fixed in the polymer matrix. Subsequent removal of the coating with entrapped contaminants results in some degree of surface decontamination. Here we report the development and investigation of a smart, decontaminating coating developed for uranium and plutonium.

As biomarker discovery takes centre-stage, the role of immunohistochemistry within that process is increasing. At the same time, the number of antibodies being produced for “research use” continues to rise and it is important that antibodies to be used as biomarkers are validated for specificity and sensitivity before use. This guideline seeks to provide a stepwise approach for the validation of an antibody for immunohistochemical assays, reflecting the views of a consortium of academic and pharmaceutical based histopathology researchers. We propose that antibodies are placed into a tier system, level 1–3, based on evidence of their usage in immunohistochemistry, and that the degree of validation required is proportionate to their place on that tier.

THE goodwill debate has been going on for many years. The problem, suggests Neil Gray, is not so much establishing the existence of goodwill as arriving at its value.

Polyethylene simultaneously functionalized with both pyrene labels and amine quencher groups has been studied to determine the extent to which self-organization and segregation of functional groups occurred during formation of a surface-bifunctionalized polymer. By measuring pyrene fluorescence in the presence of surface-bound amine quencher, pyrene fluorescence after the surface bound quenchers had been protonated, and the total amount of polymer-bound pyrene based on the amount of quenching seen with a large excess of an external quencher, we have been able to show that the mixture of functional groups at the surface is not highly segregated. The suggested integrated morphology was further supported by studies where the ratio of pyrene to internal quencher was varied over approximately 2 orders of magnitude. These studies of a bifunctional surface-modified polymer also showed that the percentage of bound pyrene that was internally quenched varied in a roughly linear way with the molar ratio of pyrene to internal quencher and that mild annealing did not change the observed two-dimensional morphology.