Measure and Probability in Cosmology

General relativity has a Hamiltonian formulation, which formally provides a canonical (Liouville) measure on the space of solutions. In ordinary statistical physics, the Liouville measure is used to compute probabilities of macrostates, and it would seem natural to use the similar measure arising in general relativity to compute probabilities in cosmology, such as the probability that the universe underwent an era of inflation. Indeed, a number of authors have used the restriction of this measure to the space of homogeneous and isotropic universes with scalar field matter (minisuperspace)---namely, the Gibbons-Hawking-Stewart measure---to make arguments about the likelihood of inflation. We argue here that there are at least four major difficulties with using the measure of general relativity to make probability arguments in cosmology: (1) Equilibration does not occur on cosmological length scales. (2) Even in the minisuperspace case, the measure of phase space is infinite and the computation of probabilities depends very strongly on how the infinity is regulated. (3) The inhomogeneous degrees of freedom must be taken into account (we illustrate how) even if one is interested only in universes that are very nearly homogeneous. The measure depends upon how the infinite number of degrees of freedom are truncated, and how one defines "nearly homogeneous." (4) In a universe where the second law of thermodynamics holds, one cannot make use of our knowledge of the present state of the universe to "retrodict" the likelihood of past conditions.Comment: 43 pages, 2 figure

Is it time to reappraise blood pressure thresholds and targets? Statement from the international society of hypertension - a global perspective

No abstract available

Inter-domain dynamics in the chaperone SurA and multi-site binding to its outer membrane protein clients

The periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis. E. coli SurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but its mechanisms of client binding and chaperone function have remained unclear. Here, we use chemical cross-linking, hydrogen-deuterium exchange mass spectrometry, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and interrogate the role of conformational dynamics in OMP recognition. We demonstrate that SurA samples an array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested in the SurA crystal structure. OMP binding sites are located primarily in the core domain, and OMP binding results in conformational changes between the core/P1 domains. Together, the results suggest that unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between domains assisting OMP recognition, binding and release

Analytic frameworks for assessing dialogic argumentation in online learning environments

Over the last decade, researchers have developed sophisticated online learning environments to support students engaging in argumentation. This review first considers the range of functionalities incorporated within these online environments. The review then presents five categories of analytic frameworks focusing on (1) formal argumentation structure, (2) normative quality, (3) nature and function of contributions within the dialog, (4) epistemic nature of reasoning, and (5) patterns and trajectories of participant interaction. Example analytic frameworks from each category are presented in detail rich enough to illustrate their nature and structure. This rich detail is intended to facilitate researchers’ identification of possible frameworks to draw upon in developing or adopting analytic methods for their own work. Each framework is applied to a shared segment of student dialog to facilitate this illustration and comparison process. Synthetic discussions of each category consider the frameworks in light of the underlying theoretical perspectives on argumentation, pedagogical goals, and online environmental structures. Ultimately the review underscores the diversity of perspectives represented in this research, the importance of clearly specifying theoretical and environmental commitments throughout the process of developing or adopting an analytic framework, and the role of analytic frameworks in the future development of online learning environments for argumentation

Second harmonic generation response by gold nanoparticles at the polarized water/2-octanone interface: from dispersed to aggregated particles

Gold nanoparticles with a diameter of approximately 20 nm have been observed at the polarized water/2-octanone interface by the nonlinear optical technique of second harmonic generation. Electric field induced adsorption of the gold particles at this liquid/liquid interface is clearly observed and confirms that these are negatively charged. The process is quasi-reversible at high potential sweep rates, but aggregation at the interface is observed at slower sweep rates through the loss of the nonlinear optical signal. The time evolution of the second harmonic signal is also reported during potential step experiments. After a rapid increase due to adsorption, a continuous decrease in the nonlinear optical signal intensity is observed due to aggregation of the particles into large islands at the interface. Diffusion of these large islands at the interface was observed for a longer timescale through large signal fluctuations

Literary ethnography of evidence-based healthcare : accessing the emotions of rational-technical discourse

In this article I revisit the idea of literary ethnography (proposed by Van de Poel-Knottnerus and Knottnerus, 1994) as a method for investigating social phenomena constituted principally through literature. I report the use of this method to investigate the topic of evidence-based healthcare, EBHC. EBHC is a field of discourse much built upon a dichotomy between rationality and emotionality. In this context literary ethnography, a particular type of discourse analysis, is valuable for allowing researchers to bring the emotional currents of technical-rational discourse into conscious awareness. In such discourses, emotions are not written out by name. The researcher must discern emotional phenomena by experiencing the discourse, and (try to) bring them into intelligible expression. As I clarify this process I develop Van de Poel-Knottnerus and Knottnerus’ method theoretically, look to destabilise the rationalityemotionality dichotomy foundational to discourse around EBHC, and so transgress its conventional lines of thought.PostprintPeer reviewe

Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

Arteries from young healthy animals respond to chronic changes in blood flow and blood pressure by structural remodeling. We tested whether the ability to respond to decreased (-90%) or increased (+100%) blood flow is impaired during the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats, a model for an upregulated endothelin-1 system. Mesenteric small arteries (MrA) were exposed to low blood flow (LF) or high blood flow (HF) for 4 or 7 weeks. The bioavailability of vasoactive peptides was modified by chronic treatment of the rats with the dual neutral endopeptidase (NEP)/endothelin-converting enzyme (ECE) inhibitor SOL1. After 3 or 6 weeks of hypertension, the MrA showed hypertrophic arterial remodeling (3 weeks: media cross-sectional area (mCSA): 10 +/- 1 x 10(3) to 17 +/- 2 x 10(3) mu m(2); 6 weeks: 13 +/- 2 x 10(3) to 24 +/- 3 x 10(3) mu m(2)). After 3, but not 6, weeks of hypertension, the arterial diameter was increased (empty set: 385 +/- 13 to 463 +/- 14 mu m). SOL1 reduced hypertrophy after 3 weeks of hypertension (mCSA: 6 x 10(3) +/- 1 x 10(3) mu m(2)). The diameter of the HF arteries of normotensive rats increased (empty set: 463 +/- 22 mu m) but no expansion occurred in the HF arteries of hypertensive rats (empty set: 471 +/- 16 mu m). MrA from SOL1-treated hypertensive rats did show a significant diameter increase (empty set: 419 +/- 13 to 475 +/- 16 mu m). Arteries exposed to LF showed inward remodeling in normotensive and hypertensive rats (mean empty set between 235 and 290 mu m), and infiltration of monocyte/ macrophages. SOL1 treatment did not affect the arterial diameter of LF arteries but reduced the infiltration of monocyte/ macrophages. We show for the first time that flow-induced remodeling is impaired during the development of DOCA-salt hypertension and that this can be prevented by chronic NEP/ECE inhibition. Hypertension Research (2012) 35, 1093-1101; doi:10.1038/hr.2012.94; published online 12 July 201

Transgenic Mice Over-Expressing ET-1 in the Endothelial Cells Develop Systemic Hypertension with Altered Vascular Reactivity

Endothelin-1 (ET-1) is a potent vasoconstrictor involved in the regulation of vascular tone and implicated in hypertension. However, the role of small blood vessels endothelial ET-1 in hypertension remains unclear. The present study investigated the effect of chronic over-expression of endothelial ET-1 on arterial blood pressure and vascular reactivity using transgenic mice approach. Transgenic mice (TET-1) with endothelial ET-1 over-expression showed increased in ET-1 level in the endothelial cells of small pulmonary blood vessels. Although TET-1 mice appeared normal, they developed mild hypertension which was normalized by the ETA receptor (BQ123) but not by ETB receptor (BQ788) antagonist. Tail-cuff measurements showed a significant elevation of systolic and mean blood pressure in conscious TET-1 mice. The mice also exhibited left ventricular hypertrophy and left axis deviation in electrocardiogram, suggesting an increased peripheral resistance. The ionic concentrations in the urine and serum were normal in 8-week old TET-1 mice, indicating that the systemic hypertension was independent of renal function, although, higher serum urea levels suggested the occurrence of kidney dysfunction. The vascular reactivity of the aorta and the mesenteric artery was altered in the TET-1 mice indicating that chronic endothelial ET-1 up-regulation leads to vascular tone imbalance in both conduit and resistance arteries. These findings provide evidence for the role of spatial expression of ET-1 in the endothelium contributing to mild hypertension was mediated by ETA receptors. The results also suggest that chronic endothelial ET-1 over-expression affects both cardiac and vascular functions, which, at least in part, causes blood pressure elevation

'If you had only listened carefully...':the discursive construction of emerging leadership in a UK all-women management team

Increasingly, feminist linguistic research has adopted a discursive perspective to learn how women and men 'do' leadership in gendered ways. 'Women' as a social category is made relevant to this study by virtue of the lack of female senior leaders in UK businesses (Sealy and Vinnicombe, 2013). Much previous research has analysed leadership discourse in mixed gender groups, relying on theories that imply comparisons between men and women. Using an Interactional Sociolinguistic approach, this study aims to learn more about how women perform leadership in the absence of men by analysing the spoken interactions of a women-only team who were engaged in a competitive leadership task. The analysis reveals that the women accomplish leadership in multiple and complex ways that defy binary gendered classifications. Nonetheless, there is a distinctive gendered dynamic to the team's interactions which, it is argued, might be disadvantageous to women aspiring to senior positions