A Post-American World? Assessing the Cognitive and Attitudinal Impacts of Challenges to American Exceptionalism

A number of voices have emerged in U.S. political discourse questioning the legitimacy of American exceptionalism, suggesting we are in a “post-American world.” Our research examines the effects that political messages that explicitly challenge American exceptionalism can have on U.S. public opinion. Drawing upon social identity theory, we find that explicit challenges to American exceptionalism significantly impact Americans’ views toward their own nation, their willingness to denigrate foreign publics, and their broader foreign policy preferences

Make no exception, save one: American exceptionalism, the American presidency, and the age of Obama

This paper explores the circumstances under which U.S. presidents have invoked the idea of American exceptionalism in major speeches to the nation and how the invocation of this concept has culminated during the Obama presidency. To explore these dynamics, we conducted a content analysis of all major domestic presidential addresses since the end of World War II. We find that U.S. presidents have become increasingly likely to invoke American exceptionalism, particularly after the end of the Cold War, and that in times of national crises, American exceptionalism becomes most pronounced in U.S. presidential discourse. Moreover, we demonstrate the overwhelming propensity of President Obama, relative to his predecessors, to emphasize American exceptionalism in his public communications. The reason, we argue, has to do with the double-crisis nature of his presidency—two major wars and a recession—in addition to the racial bind that he has been forced to overcome throughout his presidency. We reflect on the implications of these findings for politicians, in particular racial and other minorities, as well as the broader American public

Australian Strawberry Good Practice Guide

The Australian Strawberry Good Practice Guide has been developed as part of the Australian Strawberry Industry Development Program. This program is funded by Hort Innovation, using the strawberry research and development levy and contributions from the Australian Government. Hort Innovation is the grower owned, not-for-profit research and development corporation for Australian horticulture

Facile synthesis of organically synthesized porous carbon using a commercially available route with exceptional electrochemical performance

Organically synthesized porous carbon (OSPC) is a subclass of conjugated microporous polymer materials that have shown potential applications as anodes in ion batteries. However, a challenging, low-yielding, multistep synthetic route (the A method) has hindered further exploration of this exciting family. Here, OSPC-1 has been synthesized via an alternative, efficient one-pot method from commercially available reagents (the B method), hereafter referred to as OSPC-1b in contrast to OSPC-1a, where it is synthesized via the A method. Characterization revealed the same polymer structure and the highest surface area to date of an OSPC (or OSPC analogue) family member for OSPC-1b with 909 m2 g–1. OSPC-1b was tested as an anode for Li-ion batteries, demonstrating the same high capacity, fast charging, resistance to degradation, and inhibition of the formation of dangerous lithium dendrites as OSPC-1a. Furthermore, the electrochemical properties of OSPC-0 were evaluated for the first time, agreeing with previously predicted values, giving scope for the design and targeting of specific properties

Phosphatidylinositide 3-kinase (PI3K) and PI3K-related kinase (PIKK) activity contributes to radioresistance in thyroid carcinomas.

Anaplastic (ATC) and certain follicular thyroid-carcinomas (FTCs) are radioresistant. The Phosphatidylinositide 3-kinase (PI3K) pathway is commonly hyperactivated in thyroid-carcinomas. PI3K can modify the PI3K-related kinases (PIKKs) in response to radiation: How PIKKs interact with PI3K and contribute to radioresistance in thyroid-carcinomas is unknown. Further uncertainties exist in how these interactions function under the radioresistant hypoxic microenvironment. Under normoxia/anoxia, ATC (8505c) and FTC (FTC-133) cells were irradiated, with PI3K-inhibition (via GDC-0941 and PTEN-reconstitution into PTEN-null FTC-133s) and effects on PIKK-activation, DNA-damage, clonogenic-survival and cell cycle, assessed. FTC-xenografts were treated with 5 × 2 Gy, ± 50 mg/kg GDC-0941 (twice-daily; orally) for 14 days and PIKK-activation and tumour-growth assessed. PIKK-expression was additionally assessed in 12 human papillary thyroid-carcinomas, 13 FTCs and 12 ATCs. GDC-0941 inhibited radiation-induced activation of Ataxia-telangiectasia mutated (ATM), ATM-and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Inhibition of ATM and DNA-PKcs was PI3K-dependent, since activation was reduced in PTEN-reconstituted FTC-133s. Inhibition of PIKK-activation was greater under anoxia: Consequently, whilst DNA-damage was increased and prolonged under both normoxia and anoxia, PI3K-inhibition only reduced clonogenic-survival under anoxia. GDC-0941 abrogated radiation-induced cell cycle arrest, an effect most likely linked to the marked inhibition of ATR-activation. Importantly, GDC-0941 inhibited radiation-induced PIKK-activation in FTC-xenografts leading to a significant increase in time taken for tumours to triple in size: 26.5 ± 5 days (radiation-alone) versus 31.5 ± 5 days (dual-treatment). PIKKs were highly expressed across human thyroid-carcinoma classifications, with ATM scoring consistently lower. Interestingly, some loss of ATM and DNA-PKcs was observed. These data provide new insight into the mechanisms of hypoxia-associated radioresistance in thyroid-carcinoma

Targeting endothelin receptor signalling overcomes heterogeneity driven therapy failure

Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a “MITF‐high” phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance “AXL‐high” phenotype. > 50% of melanomas progress with enriched “AXL‐high” populations, and because AXL is linked to de‐differentiation and invasiveness avoiding an “AXL‐high relapse” is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF‐induced expression of endothelin 1 (EDN1). EDN1 expression is enhanced in tumours of patients on treatment and confers drug resistance through ERK re‐activation in a paracrine manner. Most importantly, EDN1 not only supports MITF‐high populations through the endothelin receptor B (EDNRB), but also AXL‐high populations through EDNRA, making it a master regulator of phenotype heterogeneity. Endothelin receptor antagonists suppress AXL‐high‐expressing cells and sensitize to BRAF inhibition, suggesting that targeting EDN1 signalling could improve BRAF inhibitor responses without selecting for AXL‐high cells

Structural Stability of Human Protein Tyrosine Phosphatase ρ Catalytic Domain: Effect of Point Mutations

Protein tyrosine phosphatase ρ (PTPρ) belongs to the classical receptor type IIB family of protein tyrosine phosphatase, the most frequently mutated tyrosine phosphatase in human cancer. There are evidences to suggest that PTPρ may act as a tumor suppressor gene and dysregulation of Tyr phosphorylation can be observed in diverse diseases, such as diabetes, immune deficiencies and cancer. PTPρ variants in the catalytic domain have been identified in cancer tissues. These natural variants are nonsynonymous single nucleotide polymorphisms, variations of a single nucleotide occurring in the coding region and leading to amino acid substitutions. In this study we investigated the effect of amino acid substitution on the structural stability and on the activity of the membrane-proximal catalytic domain of PTPρ. We expressed and purified as soluble recombinant proteins some of the mutants of the membrane-proximal catalytic domain of PTPρ identified in colorectal cancer and in the single nucleotide polymorphisms database. The mutants show a decreased thermal and thermodynamic stability and decreased activation energy relative to phosphatase activity, when compared to wild- type. All the variants show three-state equilibrium unfolding transitions similar to that of the wild- type, with the accumulation of a folding intermediate populated at ∼4.0 M urea

Vitamin D Binding Protein and Monocyte Response to 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D: Analysis by Mathematical Modeling

Vitamin D binding protein (DBP) plays a key role in the bioavailability of active 1,25-dihydroxyvitamin D (1,25(OH)2D) and its precursor 25-hydroxyvitamin D (25OHD), but accurate analysis of DBP-bound and free 25OHD and 1,25(OH)2D is difficult. To address this, two new mathematical models were developed to estimate: 1) serum levels of free 25OHD/1,25(OH)2D based on DBP concentration and genotype; 2) the impact of DBP on the biological activity of 25OHD/1,25(OH)2D in vivo. The initial extracellular steady state (eSS) model predicted that 50 nM 25OHD and 100 pM 1,25(OH)2D), <0.1% 25OHD and <1.5% 1,25(OH)2D are ‘free’ in vivo. However, for any given concentration of total 25OHD, levels of free 25OHD are higher for low affinity versus high affinity forms of DBP. The eSS model was then combined with an intracellular (iSS) model that incorporated conversion of 25OHD to 1,25(OH)2D via the enzyme CYP27B1, as well as binding of 1,25(OH)2D to the vitamin D receptor (VDR). The iSS model was optimized to 25OHD/1,25(OH)2D-mediated in vitro dose-responsive induction of the vitamin D target gene cathelicidin (CAMP) in human monocytes. The iSS model was then used to predict vitamin D activity in vivo (100% serum). The predicted induction of CAMP in vivo was minimal at basal settings but increased with enhanced expression of VDR (5-fold) and CYP27B1 (10-fold). Consistent with the eSS model, the iSS model predicted stronger responses to 25OHD for low affinity forms of DBP. Finally, the iSS model was used to compare the efficiency of endogenously synthesized versus exogenously added 1,25(OH)2D. Data strongly support the endogenous model as the most viable mode for CAMP induction by vitamin D in vivo. These novel mathematical models underline the importance of DBP as a determinant of vitamin D ‘status’ in vivo, with future implications for clinical studies of vitamin D status and supplementation

The uses and abuses of power: teaching school leadership through children's literature

There are relatively few studies of how representations of teachers, schools and educational administrators in popular films and television might be, and are, used in leadership preparation. This paper seeks to add to this small body of work; it reports on an exploratory study of the representation of headteachers in contemporary children's fiction. Thirty-one texts are analysed to ascertain key themes and the major characterisations. The paper draws on children's literature scholars to argue that both the historical school story and its contemporary counterpart focus heavily on the power of the head to control the micro-world of the school. Because these fictional accounts deal with issues of power and justice more openly than many mainstream educational administration texts, this makes them particularly useful in the preparation of potential school leaders