Retroviral-mediated gene transfer of the human erythropoietin gene into a factor-dependent cell line, TF-1

The factor-dependent cell line, TF-1, established from a patient with erythroleukaemia, shows characteristics of immature erythroblasts. Addition of granulocyte-macrophage colony stimulating factor (GM-CSF) to the culture medium is required for long-term growth of the cells. Erythropoietin (Epo) can also be used to sustain TF-1 cells but for only limited periods (approximately a week). Low levels of both growth factors can act synergistically to maintain proliferation for a longer period of time than Epo alone. To eliminate the requirement of exogenous Epo for growth, TF-1 cells were co-cultured with a retroviral secreting cell line containing the human erythropoietin (hEpo) gene and a neomycin (neo) selectable marker. TF-1 cells which exhibited neo resistance (indicating infection by the retrovirus) were then grown in low concentrations of GM-CSF without the addition of Epo. Under these conditions growth of normal TF-1 cells was not sustained. The neo-resistant cells survived for more than 14 days indicating synergy between GM-CSF and the Epo synthesised by the co-cultured TF-1 cells. Radioimmunoassays performed on growth media detected concentrations up to 1 mU/ml of Epo, implying that stable integration of the retroviral vector and expression of the hEpo gene have been achieved.

PTEN Phosphatase-Independent Maintenance of Glandular Morphology in a Predictive Colorectal Cancer Model System

Organotypic models may provide mechanistic insight into colorectal cancer (CRC) morphology. Three-dimensional (3D) colorectal gland formation is regulated by phosphatase and tensin homologue deleted on chromosome 10 (PTEN) coupling of cell division cycle 42 (cdc42) to atypical protein kinase C (aPKC). This study investigated PTEN phosphatase-dependent and phosphatase-independent morphogenic functions in 3D models and assessed translational relevance in human studies. Isogenic PTEN-expressing or PTEN-deficient 3D colorectal cultures were used. In translational studies, apical aPKC activity readout was assessed against apical membrane (AM) orientation and gland morphology in 3D models and human CRC. We found that catalytically active or inactive PTEN constructs containing an intact C2 domain enhanced cdc42 activity, whereas mutants of the C2 domain calcium binding region 3 membrane-binding loop (M-CBR3) were ineffective. The isolated PTEN C2 domain (C2) accumulated in membrane fractions, but C2 M-CBR3 remained in cytosol. Transfection of C2 but not C2 M-CBR3 rescued defective AM orientation and 3D morphogenesis of PTEN-deficient Caco-2 cultures. The signal intensity of apical phospho-aPKC correlated with that of Na/H exchanger regulatory factor-1 (NHERF-1) in the 3D model. Apical NHERF-1 intensity thus provided readout of apical aPKC activity and associated with glandular morphology in the model system and human colon. Low apical NHERF-1 intensity in CRC associated with disruption of glandular architecture, high cancer grade, and metastatic dissemination. We conclude that the membrane-binding function of the catalytically inert PTEN C2 domain influences cdc42/aPKC-dependent AM dynamics and gland formation in a highly relevant 3D CRC morphogenesis model system.

Right-Wing Violence in Germany: Assessing the Objectives, Personalities and Terror Trail of the National Socialist Underground and the State's Response to It

In the last five years the forces of organised right-wing extremism have made electoral advances across many states in contemporary Europe. Germany has not been immune and the extreme right party, the National Democratic Party of Germany won its first seat in the European Parliament since 1989. The recent successes of the extreme right pose issues for European society about tolerance and immigration policy, but this scene has also been associated with an upsurge in racially motivated political violence and acts of right-wing terrorism. Much of this violence is perpetrated by small neo-Nazi styled groups. This paper looks at the most notorious and recent of such groups to emerge in Germany, the National Socialist Underground. The paper explores the origins and personalities behind this terror cell, provides derails of its criminal activities and murder spree, and questions why it took so long for the authorities to identify the NSU.

'If we do not cut social spending, we will end up like Greece': Challenging consent to austerity through social work action

'If we do not cut social spending, we will end up like Greece'. Establishment politicians and media figures use this new ideological mantra throughout the Western world to frighten people into consenting to further neo-liberal restructuring along with cuts in social spending. This phrase and other ideologically laden assertions hide the real causes of the Greek public debt crisis. This commentary challenges the dominant discourse by contextualizing the Greek case within the larger global neo-liberal restructuring processes and then, drawing upon Gramsci's concept of the organic intellectual, proposes ways that the members of the Professional Association of Social Workers (PASW) can engage in a war of ideas and action, as organic intellectuals, to delegitimize the dominant discourse, which seeks consent for social spending cuts and further neo-liberal restructuring of society. © The Author(s) 2013.

Cities and The Spirit Level: Reasserting the Public Interest in Planning Governance

Urban planning in Europe has its roots in social reform movements for reform of the 18th and 19th centuries and in the UK evolved into the state-backed comprehensive planning system established as a pillar of the welfare state in 1947. This new planning system played a key role in meeting key social needs of the early post-war period, through, for example, an ambitious new town programme. However, from the late 1970s onwards the main priorities of the planning system have shifted as the UK state has withdrawn support for welfare and reasserted market values. One consequence of this has been an increased inequality in access to many of the resources that planning seeks to regulate, including affordable housing, local services and environmental quality.
Drawing on evidence from recent literature on equality, including Wilkinson and Pickett’s The Spirit Level this paper will question the role of planning in an era of post-politics and a neo-liberal state. It will review some of the consequences for the governance and practice of planning and question what this means for the core values of the planning profession. Finally, the paper will discuss the rise of the Healthy Urban Planning Movement in the US and Europe and ask whether this provides any potential for reasserting the public interest in planning process.

Short comment: To Nail a Jellyfish? Finding a progressive agenda for EU anti-discrimination law

The title of this short (about 4500 words) intervention translates to "To Nail a Jellyfish? Finding a progressive agenda for EU anti-discrimination law". I engage with those criticising EU anti-discrimination law as yet another emanation of the EU's "neo-liberal" nature which fails to establish a viable social policy regime. I criticise this in two directions. First, I take issue with the theory that anti-discrimination law and policy has to be part of social policy. Actually, the field has a mission which differs from social policy, in that it addresses disadvantage resulting from othering, combating stereotypes as well as promoting accomodation of difference. Second, I show how the critique of judicialisation of policy is not unique to anti-discrimination law and policy. The so called turn to rights based employment law has been criticised under this mantra by those who fear that collective labour law mechanisms will become less prevalent. Further, those who have engaged with anti-discrimination law for a much longer time than those criticising it have also devised means to overcome the individualistic tendencies of rights adjudication. They have (partly successfully) argued in favour of establishing equality bodies and creating positive obligations. Thus, the critique neglects the field it takes on, and does not accept the fact that anti-discrimination law and policy must be considered a field in its own right instead of the servant of social law and policy.
Now, this is more a summary than an abstract - since I realise that not everyone reads German.

Ageing through Austerity: critical perspectives from Ireland

The book’s main contribution is the bringing together of varied discourses concerning the social policy impact of ageing within the context of fiscal austerity. As the editors rightly state, the economic recession has sharpened the focus of governments on the implication of demographic ageing. It is vital therefore, that the social policy implications of societal ageing are studied and understood within a wider political economy of austerity. Of course the fiscal crisis of the 1970s and the ensuing first wave of neo-liberalism in the Anglo-Saxon countries [in the 1980s] gave us a foretaste of the various ways in which the public burden thesis has been applied with great force to the older population. This recession is different, certainly in Ireland, but a combination of neo-liberal ideology and neo-classical economics is enforcing severe budgetary constraint on a range of countries (within and outside of the Eurozone) in the name of funding deficits. Policy makers appear to be disinterested in both the origins of the 2008 financial crisis and the distributional consequences of their austerity policies. In the absence of official concern social science research has a key role to play.

Whey proteins have beneficial effects on intestinal enteroendocrine cells stimulating cell growth and increasing the production and secretion of incretin hormones

Whey protein has been indicated to curb diet-induced obesity, glucose intolerance and delay the onset of type 2 diabetes mellitus. Here the effects of intact crude whey, intact individual whey proteins and beta-lactoglobulin hydrolysates on an enteroendocrine (EE) cell model were examined. STC-1 pGIP/neo cells were incubated with several concentrations of yogurt whey (YW), cheese whey (CW), beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and bovine serum albumin (BSA). The findings demonstrate that BLG stimulates EE cell proliferation, and also GLP-1 secretion (an effect which is lost following hydrolysis with chymotrypsin or trypsin). ALA is a highly potent GLP-1 secretagogue which also increases the intracellular levels of GLP-1. Conversely, whey proteins and hydrolysates had little impact on GIP secretion. This appears to be the first investigation of the effects of the three major proteins of YW and CW on EE cells. The anti-diabetic potential of whey proteins should be further investigated.

The fate of chemoresistance in triple negative breast cancer (TNBC)

Background: Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype. 
Scope of Review: How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed. 
Major conclusions: Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome. 
General Significance: Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy

The Complete Works of John Milton: Volume III: The Shorter Poems (826pp.)

Stephen B. Dobranski, Milton Quarterly 49.3 (October, 2015), 181-4:

'By addressing classical and neo-Latin works with which Milton's poems appear to engage, Haan has pursued something unattempted yet. Her erudite and engaging commentary on the Poemata is the most extensive and impressive that I have encountered in any edition ... Haan's discussion of Milton's Poemata - including the Testimonia, the one Italian and four Latin encomia by the poet's acquaintances published in 1645 and 1673 - is remarkably detailed and well-researched. In these sections, readers learn, for example, how Milton's Epitaphium Damonis borrows from both classical writers (Theocritus, Moschus) and contemporary models (Castiglione, Zanchi) while transcending all of them through a pattern of resurrection motifs. Or, readers can discover affinities between Milton's lament on the death of the Bishop of Ely and a poem by the Italian humanist Hieronymo Aleander, Jr., or learn about the connections between Milton's Elegia Quinta and George Buchanan's Maiae Calendae ... The Shorter Poems is a scholarly achievement of the highest order.'

Noam Reisner, Review of English Studies 65 (2014), 744-5:
‘Haan shines with her Neo-Latinist expertise by offering a vivid separate introduction to the Latin poems, which sets up Milton’s poemata specifically within the Neo-Latin contexts of the seventeenth century, thereby dispelling any remaining view of these poems as juvenilia (a view which results from reading the poems chronologically). … The present volume will instantly establish itself as the definitive resource for any reader interested in Milton’s shorter poems, and it is scarcely imaginable that it will ever be eclipsed or be in need of replacing. Its contribution is important in all areas, especially in providing for the first time in a single volume truly valuable documents which can teach us a lot more about Milton’s poetic development than simply reading the poems in chronological sequence. But perhaps, this edition’s greatest achievement is the way in which it succeeds in giving Milton’s Latin poems the pride of place they have long deserved as fully integral to Milton’s complete poetic imagination. Haan’s specific achievement in this regard is less in updating the translations than in providing a different context through which to look at the Latin poems themselves. Haan’s detailed commentaries set the Latin poems in a completely fresh light which looks beyond the obvious classical references and allusions, noted by Carey and many other editors, to Milton’s complex engagement with the Neo-Latin literary culture of his time. It is this aspect of the volume, more than anything else, which vindicates its essentialness.'

The Deconstructed Church: Understanding Emerging Christianity

The Emerging Church Movement (ECM) is a reform movement within Western Christianity that reacts against its roots in conservative evangelicalism by “de-constructing” contemporary expressions of Christianity. Emerging Christians see themselves as overturning out-dated interpretations of the bible, transforming hierarchical religious institutions, and re-orientating Christianity to step outside the walls of church buildings toward working among and serving others in the “real world.”

Drawing on ethnographic observations from emerging congregations, pub churches, neo-monastic communities, conferences, online networks, in-depth interviews, and congregational surveys in the US, UK, and Ireland, this book provides a comprehensive social scientific analysis of the development and significance of the ECM. Emerging Christians are shaping a distinct religious orientation that encourages individualism, deep relationships with others, new ideas around the nature of truth, doubt, and God, and innovations in preaching, worship, Eucharist, and leadership.

Development and Validation of a Novel Lateral Flow Immunoassay (LFIA) for the Rapid Screening of Paralytic Shellfish Toxins (PSTs) from Shellfish Extracts

A single-step lateral flow immunoassay (LFIA) was developed and validated for the rapid screening of paralytic shellfish toxins (PSTs) from a variety of shellfish species, at concentrations relevant to regulatory limits of 800 μg STX-diHCl equivalents/kg shellfish meat. A simple aqueous extraction protocol was performed within several minutes from sample homogenate. The qualitative result was generated after a 5 min run time using a portable reader which removed subjectivity from data interpretation. The test was designed to generate noncompliant results with samples containing approximately 800 μg of STX-diHCl/kg. The cross-reactivities in relation to STX, expressed as mean ± SD, were as follows: NEO: 128.9% ± 29%; GTX1&4: 5.7% ± 1.5%; GTX2&3: 23.4% ± 10.4%; dcSTX: 55.6% ± 10.9%; dcNEO: 28.0% ± 8.9%; dcGTX2&3: 8.3% ± 2.7%; C1&C2: 3.1% ± 1.2%; GTX5: 23.3% ± 14.4% (n = 5 LFIA lots). There were no indications of matrix effects from the different samples evaluated (mussels, scallops, oysters, clams, cockles) nor interference from other shellfish toxins (domoic acid, okadaic acid group). Naturally contaminated sample evaluations showed no false negative results were generated from a variety of different samples and profiles (n = 23), in comparison to reference methods (MBA method 959.08, LC-FD method 2005.06). External laboratory evaluations of naturally contaminated samples (n = 39) indicated good correlation with reference methods (MBA, LC-FD). This is the first LFIA which has been shown, through rigorous validation, to have the ability to detect most major PSTs in a reliable manner and will be a huge benefit to both industry and regulators, who need to perform rapid and reliable testing to ensure shellfish are safe to eat.

Measuring critical thinking skills and dispositions in undergraduate students

This thesis investigates critical thinking with a particular focus on measurement in undergraduate students. A higher education context was chosen because many regard critical thinking development as a primary goal for third level education. Nine studies, both cross-sectional and longitudinal in design, were conducted with undergraduate psychology students (N=387), using the California Critical Thinking Disposition Inventory (CCTDI) and the California Critical Thinking Skills Test (CCTST). Studies 1-3 revealed psychometric weaknesses in the CCTDI and revised the scale with factor analysis and reliability analysis to form the CCTDI United Kingdom revision (CCTDI-UK). Study 4 investigated convergent validity and showed significant inter-correlation between the sub-scales of the CCTDI-UK, and significant correlations with the Openness scale of the NEO Personality Inventory (NEO PI-R). The study also provided evidence for improvement in scores on three of the six sub-scales in the CCTDI-UK (Truth-Seeking, Inquisitiveness, Open-Mindedness) during the course of an undergraduate degree. Study 5 explored a two factor structure for critical thinking dispositions. Study 6 used reliability analysis to revise the CCTST to produce the CCTST-UK. Study 7 showed that the CCTST-UK had a moderate correlation with degree attainment and a slightly higher correlation with a test of non-verbal intelligence (Raven’s Advanced Progressive Matrices short form); in addition, the study showed that scores on the CCTST-UK improved during the course of the degree. Studies 8 and 9 investigated the potential of critical thinking for predicting degree attainment. A-levels predicted approximately 10% of the variance of degree attainment while entry level scores on the CCTST-UK predicted an additional 5%. Exit level scores on the CCTST-UK and the Inquisitive sub-scale of the CCTDI-UK were found to be predictors of degree attainment The main conclusions of the thesis were that these tests had significant potential for predicting degree attainment and that they measured a substantial proportion of the theoretical constructs identified by the major authors in critical thinking.

Understanding controls on cirque floor altitudes: insights from Kamchatka

Glacial cirques reflect former regions of glacier initiation, and are therefore used as indicators of past climate. One specific way in which palaeoclimatic information is obtained from cirques is by analysing their elevations, on the assumption that cirque floor altitudes are a proxy for climatically controlled equilibrium-line altitudes (ELAs) during former periods of small scale (cirque-type) glaciation. However, specific controls on cirque altitudes are rarely assessed, and the validity of using cirque floor altitudes as a source of palaeoclimatic information remains open to question. In order to address this, here we analyse the distribution of 3520 ice-free cirques on the Kamchatka Peninsula (eastern Russia), and assess various controls on their floor altitudes. In addition, we analyse controls on the mid-altitudes of 503 modern glaciers, currently identifiable on the peninsula, and make comparisons with the cirque altitude data. The main study findings are that cirque floor altitudes increase steeply inland from the Pacific, suggesting that moisture availability (i.e., proximity to the coastline) played a key role in regulating the altitudes at which former (cirque-forming) glaciers were able to initiate. Other factors, such as latitude, aspect, topography, geology and neo-tectonics seem to have played a limited (but not insignificant) role in regulating cirque floor altitudes, though south-facing cirques are typically higher than their north-facing equivalents, potentially reflecting the impact of prevailing wind directions (from the SSE) and/or variations in solar radiation on the altitudes at which former glaciers were able to initiate. Trends in glacier and cirque altitudes across the peninsula are typically comparable (i.e., values typically rise from both the north and south, inland from the Pacific coastline, and where glaciers/cirques are south-facing), yet the relationship with latitude is stronger for modern glaciers, and the relationship with distance to the coastline (and to a lesser degree with aspect) is notably weaker. These differences suggest that former glacier initiation (leading to cirque formation) was largely regulated by moisture availability (during winter months) and the control this exerted on accumulation; whilst the survival of modern glaciers is also strongly regulated by the variety of climatic and non climatic factors that control ablation. As a result, relationships between modern glacier mid-altitudes and peninsula-wide climatic trends are more difficult to identify than when cirque floor altitudes are considered (i.e., cirque-forming glaciers were likely in climatic equilibrium, whereas modern glaciers may not be).

A Gendered Profession

A Gendered Profession, RIBA Publications, Oct 2016

For a profession that claims to be so concerned with the needs of society, the continuing gender imbalance in architectural education and practice is a difficult subject. Difficult, because it’s been stagnant for some thirty years. This book seeks to change that.
Beyond the profession, the emergence of fourth wave feminism has broken a twenty-year drought in the discourse[1]. A new generation of feminist critique is emerging, characterised by a broader civic commitment, one fuelled by the recognition that time and again, women and minorities have been the first casualties of neo-liberalism.
Whereas after World War II the architectural profession rallied around its obligation to fulfil a social need, today architecture has all but capitulated its absolute servitude to capitalism. Recognising that feminist thinking is a meaningful response to the inequalities of capitalism, A Gendered Profession will be a forum for a discussion about the failure of our profession – one that is so explicitly concerned with the design of inclusive environments – to resolve its own inequalities. Contributions have been sought and responses elicited from all corners of the discipline to propose strategies, attitudes and solutions to this crisis in representation.
At stake is more than just the lack of female representation. Male architects suffer from the same ingrained mechanisms of gender stereotyping, obliged to place professional commitments above those to their family and children. And while three quarters of lesbian, gay, bisexual and transsexual architects report being comfortable about being open about their sexuality in the workplace, that number drops to just sixteen per cent when on the building site.
A Gendered Profession will aim to perform a diagnostic check of the architecture profession from one end of the spectrum to the other. Whereas much has been written on feminism and architecture, the majority is produced exclusively by women. A Gendered Profession has worked hard towards gender parity in both its contributions and editorial structure and therefore does not limit its understanding of gender to an either/or analogue. The chapters featured in the book are written by artists, academics, practitioners and students.
Through its diverse authorship, this book will provide the first ever attempt to move the debate beyond the tradition of gender-partitioned diagnostic or merely critical discourse on the gender and wider inclusivity debate towards something more propositional, actionable and transformative.