Energy transitions and mass publics: manipulating public perception and ideological entrenchment in Japanese nuclear power policy

How can leaders successfully craft energy or climate policy to support an initiative that citizens oppose? This paper considers this challenge from a change management perspective applied to public governance. It first draws on change management theory to develop a framework for altering mass public perspectives. The framework consists of four phases: i) problematizing the issue, ii) laying a foundation for change, iii) reshaping perspectives, and iv) entrenching support. Drawing from the insights gleaned from the establishment of Japan's nuclear power program, the paper further argues that in order to succeed in mass perceptual change, policymakers must first clearly understand the contextual environment in which the policy is being formulated. In doing so, policymakers will be better able to customize policy design to appeal to stakeholder perceptions and sentiments. Although the context of this paper is the perceptual modification of public opinion to support nuclear power, the authors suggest that the same framework can be applied to perceptual modification of any policy that the general public might be opposed to. In the energy sector, this could apply to fostering a transition to renewable energy as easily as it applies to nurturing nuclear power development. However, the Japanese case puts forth a caveat in this regard, there is evidence that the mindsets of the Japanese policymakers were predisposed to advocacy of nuclear power and once policymakers commit to a technological trajectory, it is hard to engender a change of course. Therefore, the article concludes by speculating on how the perceptions of policymakers might be similarly altered through efforts from the alternative energy sector to foster policy change

Phosphorylation of androgen receptors at serine 515 is a potential prognostic marker for triple negative breast cancer

1.7 million cases of breast cancer are diagnosed every year with 522,000 deaths. Molecular classifications of breast cancer have resulted in improved treatments. However, treatments for triple negative breast cancer (TNBC) are lacking. Analysis of molecular targets for TNBC is a priority. One potential candidate is androgen receptor (AR) phosphorylation. This study assessed the role of AR phosphorylation at ser81/ser515 and their two upstream effectors, cyclin-dependent kinase 1 (pCDK1) and extracellular-regulated kinase 1/2 (pERK1/2) in 332 ductal breast cancer patients by immunohistochemistry. pERK1/2 combined with AR-515 associated with improved cancer-specific survival (CSS, p = 0.038), decreased size (p = 0.001), invasive grade (p < 0.001), necrosis (p = 0.003), b-lymphocytes (p = 0.020), molecular subtype (p < 0.001) and estrogen receptor (ER)/progesterone receptor (PR)-status (p < 0.001). The cohort was therefore stratified into ER+ve and ER-ve patients. In ER+ve tumours, pERK1/2 combined with AR-515 associated with improved CSS (p = 0.038), smaller size (p = 0.004), invasive grade (p = 0.001), decreased b-lymphocytes (p = 0.013) and increased plasma cells (p = 0.048). In contrast, in TNBC patients, phosphorylation of AR-515 associated with poorer CSS (p = 0.007). pERK1/2 combined with AR-515 associated with decreased inflammation (p = 0.003), increased tumour stroma (p = 0.003) and tumour budding (p = 0.011), with trends towards decrease CSS (p = 0.065) and macrophage levels (p = 0.093). In Conclusions, AR-515 may be an important regulator of inflammation in breast cancer potential via ERK1/2 phosphorylation. AR-515 is a potential prognostic marker and therapeutic target for TNBC

Anti-Hispanic prejudice drives opposition to immigration in the U.S.

Last June, the U.S. Senate passed a comprehensive immigration bill that would give legal status to 11 million undocumented migrants, but this bill has remained stalled in the House of Representatives, reflecting the anti-immigration sentiments of many Americans. New research from Todd K. Hartman, Benjamin J. Newman, and C. Scott Bell investigates why so many are against immigration reform, and the role played by racial prejudice against Hispanics. Using surveys designed to detect anti-Hispanic prejudice, they find that white Americans react very differently to law-violating behaviors whether they are committed by Hispanic immigrants or not, suggesting a significant and persistent bias against them

Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, while the cerebral metabolic rate for oxygen (CMRO2) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, ten male cyclists cycled in the heat for ~2 h with (control) and without fluid replacement (dehydration) while internal (ICA) and external (ECA) carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate the CMRO2. In study 2 (8 males), middle cerebral artery blood velocity (MCA Vmean) was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, ICA flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced oxygen and glucose extraction (P < 0.05). ECA flow increased for one hour but declined prior to exhaustion. Fluid ingestion maintained cerebral and extra-cranial perfusion throughout non-fatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extra-cranial perfusion. Thus fatigue is related to reduction in CBF and extra-cranial perfusion rather than in CMRO2.The study was supported by a grant from the Gatorade Sports Science Institute, PepsiCo Inc, USA

Combinatorial drug discovery in nanoliter droplets

Combinatorial drug treatment strategies perturb biological networks synergistically to achieve therapeutic effects and represent major opportunities to develop advanced treatments across a variety of human disease areas. However, the discovery of new combinatorial treatments is challenged by the sheer scale of combinatorial chemical space. Here, we report a high-throughput system for nanoliter-scale phenotypic screening that formulates a chemical library in nanoliter droplet emulsions and automates the construction of chemical combinations en masse using parallel droplet processing. We applied this system to predict synergy between more than 4,000 investigational and approved drugs and a panel of 10 antibiotics against Escherichia coli, a model gram-negative pathogen. We found a range of drugs not previously indicated for infectious disease that synergize with antibiotics. Our validated hits include drugs that synergize with the antibiotics vancomycin, erythromycin, and novobiocin, which are used against gram-positive bacteria but are not effective by themselves to resolve gram-negative infections. Keywords: high-throughput screening; nanoliter droplet; drug synergy; antibiotics; small molecule

Examination of Edge Effects with Different Storage Conditions of Preplated Dimethyl Sulfoxide Nanospots in ChemLib 1,536- and 3,456-Well Assay-Ready Plates

For ultra-high-throughput screening, 10–30 nl of compound dissolved in 75% dimethyl sulfoxide (DMSO)/25% water (vol/vol) is spotted into 1,536- and 3,456-well ChemLib™ plates (Aurora Biotechnologies, Carlsbad, CA) and stored appropriately for a short time before screening. Although this practice eliminates the compound plating bottleneck, plated volumes of DMSO slowly evaporate from assay wells if plates are not properly stored in the interim. Since many assays are sensitive to DMSO concentrations, even slight evaporation may cause intra-plate variation and thus decrease assay quality. Using a cytochrome P450 3A4 Vivid® Blue assay (Invitrogen, Carlsbad), we investigated the rate, pattern, and quantity of evaporation over a 1-year time frame to identify best practices for long-term (i.e., 6 months or greater) storage of assay-ready compound plates. Our findings regarding evaporation at plate edges indicate that nanospots preplated in ChemLib 1,536- or 3,456-well plates are best stored at −80°C, in a bag, with or without the outer evaporation wells filled or at −20°C, in a bag, with evaporation wells filled.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63203/1/adt.2008.169.pd