The 'Parekh Report' - national identities with nations and nationalism

‘Multiculturalists’ often advocate national identities. Yet few study the ways in which ‘multiculturalists’ do so and in this article I will help to fill this gap. I will show that the Commission for Multi-Ethnic Britain’s report reflects a previously unnoticed way of thinking about the nature and worth of national identities that the Commission’s chair, and prominent political theorist, Bhikhu Parekh, had been developing since the 1970s. This way of thinking will be shown to avoid the questionable ways in which conservative and liberal nationalists discuss the nature and worth of national identities while offering an alternative way to do so. I will thus show that a report that was once criticised for the way it discussed national identities reflects how ‘multiculturalists’ think about national identities in a distinct and valuable way that has gone unrecognised

Sequential forward and reverse transport of the Na+ Ca2+ exchanger generates Ca2+ oscillations within mitochondria

Mitochondrial Ca2+ homoeostasis regulates aerobic metabolism and cell survival. Ca2+ flux into mitochondria is mediated by the mitochondrial calcium uniporter (MCU) channel whereas Ca2+ export is often through an electrogenic Na+–Ca2+ exchanger. Here, we report remarkable functional versatility in mitochondrial Na+–Ca2+ exchange under conditions where mitochondria are depolarised. Following physiological stimulation of cell-surface receptors, mitochondrial Na+–Ca2+ exchange initially operates in reverse mode, transporting cytosolic Ca2+ into the matrix. As matrix Ca2+ rises, the exchanger reverts to its forward mode state, extruding Ca2+. Transitions between reverse and forward modes generate repetitive oscillations in matrix Ca2+. We further show that reverse mode Na+–Ca2+ activity is regulated by the mitochondrial fusion protein mitofusin 2. Our results demonstrate that reversible switching between transport modes of an ion exchanger molecule generates functionally relevant oscillations in the levels of the universal Ca2+ messenger within an organelle

Topics concerning state variable feedback in automatic control systems. Part 1 - Specification. Part 2 - Sensitivity. Part 3 - Intentional nonlinearities. Part 4 - Unavailable states

Specifications, sensitivity, intentional nonlinearities, and unavailable states concerned with state variable feedback in automatic control system

Cruciate retaining versus posterior-stabilized total knee arthroplasty: a short-term comparative study

Background: Total knee arthroplasty has got excellent results. Among the techniques (posterior-stabilized vs posterior cruciate retaining total knee arthroplasty) it is unclear whether one design has superior outcome over another. The purpose of the present study was to directly compare clinical and radiological outcomes of these two designs.Methods: A prospective study involving 36 patients who received a cruciate-retaining implant were compared to 30 patients who received posterior-stabilized prosthesis. At 3 months follow-up time clinical and radiological evaluation done and results were analyzed.Results: At 3 months follow-up time mean knee society scores improved from 49.9/46.9 (objective/subjective score) points to 80.9/82.5 points in the cruciate-retaining group and from 48.2/43 (objective/subjective score) points to 80.4/80.2 points in the posterior-stabilized group. The ranges of motion was 117.2° (range, 90° to 130°) and 125.3° (range, 100° to 140°) in the cruciate-retaining and posterior-stabilized group respectively, at 3 month follow-up. One patient had post-operatively periprosthetic fracture reported after 2 weeks (treated conservatively), one had superficial infection (treated with dressing) and one patient with superfical infection required debridement.Conclusions: This study did not conclusively demonstrate the superiority of one knee design over the other, suggesting that the choice of implant should be based on surgeon preference, patients knee dimensions, pre-op knee deformity and existing pathology of the posterior cruciate ligament

Adam Smith and Colonialism

In the context of debates about liberalism and colonialism, the arguments of Adam Smith have been taken as illustrative of an important line of anti-colonial liberal thought. The reading of Smith presented here challenges this interpretation. It argues that Smith’s opposition to colonial rule derived largely from its impact on the metropole, rather than on its impact on the conquered and colonised; that Smith recognised colonialism had brought ‘improvement’ in conquered territories and that Smith struggled to balance recognition of moral diversity with a universal moral framework and a commitment to a particular interpretation of progress through history. These arguments have a wider significance as they point towards some of the issues at stake in liberal anti-colonial arguments more generally

Caricaturizing Freedom: Islam, Offence, and the Danish Cartoon Controversy

I argue in this paper that the publication of cartoons caricaturing Islam by Jyllands- Posten is problematic for a number of reasons. First, within liberal political theory itself, there are reasonable arguments that the depictions (at least two) perpetuate prejudice and verge on hate speech. Second, such depictions weaken the social conditions that make possible a thriving democracy (i.e., participation) by marginalizing the already marginalized. Moreover, the caricatures perpetuate an Orientalist discourse about the nature of Islam and the non-West, and hinder global intercultural dialogue and understanding between nations

Control of NFAT Isoform Activation and NFAT-Dependent Gene Expression through Two Coincident and Spatially Segregated Intracellular Ca 2+ Signals

© 2016 The Author(s) Excitation-transcription coupling, linking stimulation at the cell surface to changes in nuclear gene expression, is conserved throughout eukaryotes. How closely related coexpressed transcription factors are differentially activated remains unclear. Here, we show that two Ca2+-dependent transcription factor isoforms, NFAT1 and NFAT4, require distinct sub-cellular InsP3 and Ca2+ signals for physiologically sustained activation. NFAT1 is stimulated by sub-plasmalemmal Ca2+ microdomains, whereas NFAT4 additionally requires Ca2+ mobilization from the inner nuclear envelope by nuclear InsP3 receptors. NFAT1 is rephosphorylated (deactivated) more slowly than NFAT4 in both cytoplasm and nucleus, enabling a more prolonged activation phase. Oscillations in cytoplasmic Ca2+, long considered the physiological form of Ca2+ signaling, play no role in activating either NFAT protein. Instead, effective sustained physiological activation of NFAT4 is tightly linked to oscillations in nuclear Ca2+. Our results show how gene expression can be controlled by coincident yet geographically distinct Ca2+ signals, generated by a freely diffusible InsP3 message

National identity - A multiculturalist's approach

‘Multiculturalists’ in Britain have advocated the importance of national identity since the 1970s. Yet many claim that multiculturalists do not do this and few study how they do it. We thus do not know why and how multiculturalists in Britain advocate the importance of national identity. In this article I will examine how one of Britain’s most prominent multiculturalists, Bhikhu Parekh, has done so since the 1970s. I will show that Parekh’s way of thinking about national identity is distinct from the ways in which other prominent thinkers discuss such an identity, and valuable, as Parekh has insights into what such an identity is and why we should value it. This article will identify a previously unnoticed, distinct and valuable way of thinking about national identity, which comes from a multiculturalist in Britain

Community-engaged primary care medical education

BACKGROUND: Community-engaged medical education (CEME) requires medical schools to partner with local communities to help address community priorities, whilst enhancing the learning experiences of students. Current literature on CEME has focused on evaluating its effects on students; however, there remains a gap in exploring whether CEME initiatives can have a sustainable impact for communities. APPROACH: The Community Action Project (CAP) at Imperial College London, is an eight-week, community-engaged, quality improvement project for Year 3 medical students. Students initially consult with clinicians, patients and wider community stakeholders to understand local needs and assets, and identify a health priority to address. They then work with relevant stakeholders to design, implement and evaluate a project to help address their identified priority. EVALUATION: All CAPs (n = 264) completed in the 2019-2021 academic years were evaluated for evidence of several key areas, including community engagement and sustainability. 91% of projects evidenced a needs analysis, 71% demonstrated patient involvement in their development, and 64% demonstrated sustainable impacts from their projects. Analysis revealed the topics frequently addressed, and the formats used by students. Two CAPs are described in more detail to demonstrate their community impact. IMPLICATIONS: The CAP demonstrates how the principles of CEME (meaningful community engagement and social accountability) can lead to sustainable benefits for local communities through purposeful collaboration with patients and local communities. Strengths, limitations and future directions are highlighted

GW627368X inhibits proliferation and induces apoptosis in cervical cancer by interfering with EP4/EGFR interactive signaling

PGE2, the major product of cyclooxygenases implicated in carcinogenesis, is significantly upregulated in cervical cancer. PGE2 via prostanoid receptor EP4 stimulates proliferation and motility while inhibiting apoptosis and immune surveillance. It promotes angiogenesis by stimulating the production of pro-angiogenic factors. The present study demonstrates GW627368X, a highly selective competitive EP4 antagonist, which hinders cervical cancer progression by inhibiting EP4/Epithelial Growth Factor Receptor (EGFR) interactive signaling. GW627368X reduced Protein Kinase A (PKA) phosphorylation which in turn leads to decreased cAMP response element-binding protein (CREB) activation. Decreased PKA phosphorylation also directly enhanced Bax activity and in part reduced glycogen synthase kinase 3 (GSK3)β phosphorylation. Owing to the interactive signaling between EP4 and EGFR, GW627368X lowered EGFR phosphorylation in turn reducing Akt, Mitogen-activated Protein Kinase (MAPK) and GSK3β activity significantly. Sublethal dose of GW627368X was found to reduce the nuclear translocation of β-catenin in a time dependent manner along with time-dependent decrease in cytoplasmic as well as whole-cell β-catenin. Decreased CREB and β-catenin transcriptional activity restricts the aberrant transcription of key genes like EP4, cyclooxygenase (COX)-2, vascular endothelial growth factor and c-myc, which ultimately control cell survival, proliferation and angiogenesis. Reduced activity of EGFR resulted in enhanced expression of 15-hydroxyprostaglandin dehydrogenase increasing PGE2 degradation thereby blocking a positive feedback loop. In xenograft model, dose-dependent decrease in cancer proliferation was observed characterized by reduction in tumor mass and volume and a marked decrease in Ki67 expression. A diminished CD31 specific staining signified decreased tumor angiogenesis. Reduced expression of pAkt, pMAPK, pEGFR and COX-2 validated in vitro results. GW627368X therefore effectively inhibits tumor survival, motility, proliferation and angiogenesis by blocking EP4/EGFR interactive signaling. EP4 is a potent therapeutic target in cervical cancer and can be explored in combination with conventional therapies to attain superior outcomes and to overcome complications associated with organ toxicities, therapeutic resistance and disease relapse