The Gaussian Curvature Elastic Modulus of N-Monomethylated Dioleoylphosphatidylethanolamine: Relevance to Membrane Fusion and Lipid Phase Behavior

AbstractThe energy of intermediates in fusion of phospholipid bilayers is sensitive to κ¯m, the saddle splay (Gaussian curvature) elastic modulus of the lipid monolayers. The value κ¯m is also important in understanding the stability of inverted cubic (QII) and rhombohedral (R) phases relative to the lamellar (Lα) and inverted hexagonal (HII) phases in phospholipids. However, κ¯m cannot be measured directly. It was previously measured by observing changes in QII phase lattice dimensions as a function of water content. Here we use observations of the phase behavior of N-mono-methylated dioleoylphosphatidylethanolamine (DOPE-Me) to determine κ¯m. At the temperature of the Lα/QII phase transition, TQ, the partial energies of the two phases are equal, and we can express κ¯m in terms of known lipid monolayer parameters: the spontaneous curvature of DOPE-Me, the monolayer bending modulus κm, and the distance of the monolayer neutral surface from the bilayer midplane, δ. The calculated ratio κ¯m/κm is −0.83±0.08 at TQ ≈ 55°C. The uncertainty is due primarily to uncertainty in the value of δ for the Lα phase. This value of κ¯m/κm is in accord with theoretical expectations, including recent estimates of the value required to rationalize observations of rhombohedral (R) phase stability in phospholipids. The value κ¯m substantially affects the free energy of formation of fusion intermediates: more energy (tens of kBT) is required to form stalks and fusion pores (ILAs) than estimated solely on the basis of the bending elastic energy. In particular, ILAs are much higher in energy than previously estimated. This rationalizes the action of fusion-catalyzing proteins in stabilizing nascent fusion pores in biomembranes; a function inferred from recent experiments in viral systems. These results change predictions of earlier work on ILA and QII phase stability and Lα/QII phase transition mechanisms. To our knowledge, this is the first determination of the saddle splay (Gaussian) modulus in a lipid system consisting only of phospholipids

Leukocytes are primed in peripheral blood for activation during term and preterm labour†

We hypothesized that the priming and activation of maternal leukocytes in peripheral blood is a key component of parturition, and that inappropriate preterm priming of leukocytes might initiate preterm labour and delivery. The purpose of this study was to characterize peripheral blood leukocyte activation during human term and preterm labour. We obtained blood samples from pregnant women at term and preterm, both in labour and not in labour. Leukocytes were characterized according to cell subtype and cell surface marker expression. Additionally, we quantified leukocyte cytokine mRNA production, migratory ability and reactive oxygen species production of neutrophils and macrophages. We found that both term and preterm labour were associated with an increase in monocyte and neutrophil proportion or number—neutrophil migratory ability and cell surface marker expression indicating activation. Messenger RNA expression of IL-1β and IL-8, MCP-1 and TLR-2 was also increased. We conclude that leukocytes in peripheral blood are primed in preparation for activation during term and preterm labour, and that this may contribute to the pathophysiological events of parturition. These data may lead to novel therapies and diagnostic tools for the prevention and/or diagnosis of preterm birth

The Middle Way: East Asian masters students’ perceptions of critical argumentation in U.K. universities.

The paper explores the learning experiences of East Asian masters students in dealing with Western academic norms of critical thinking in classroom debate and assignment writing. The research takes a cultural approach, and employs grounded theory and case study methodology, the aims being for students to explain their perceptions of their personal learning journeys. The data suggest that the majority of students interviewed rejected full academic acculturation into Western norms of argumentation. They instead opted for a ‘Middle Way’ that synergizes the traditional cultural academic values held by many East Asian students with those elements of Western academic norms that are perceived to be aligned with these. This is a relatively new area of research which represents a challenge for British lecturers and students

Baryon polarization in low-energy unpolarized meson-baryon scattering

We compute the polarization of the final-state baryon, in its rest frame, in low-energy meson--baryon scattering with unpolarized initial state, in Unitarized BChPT. Free parameters are determined by fitting total and differential cross-section data (and spin-asymmetry or polarization data if available) for $pK^-$, $pK^+$ and $p\pi^+$ scattering. We also compare our results with those of leading-order BChPT

Gauge and Scheme Dependence of Mixing Matrix Renormalization

We revisit the issue of mixing matrix renormalization in theories that include Dirac or Majorana fermions. We show how a gauge-variant on-shell renormalized mixing matrix can be related to a manifestly gauge-independent one within a generalized ${\bar {\rm MS}}$ scheme of renormalization. This scheme-dependent relation is a consequence of the fact that in any scheme of renormalization, the gauge-dependent part of the mixing-matrix counterterm is ultra-violet safe and has a pure dispersive form. Employing the unitarity properties of the theory, we can successfully utilize the afore-mentioned scheme-dependent relation to preserve basic global or local symmetries of the bare Lagrangian through the entire process of renormalization. As an immediate application of our study, we derive the gauge-independent renormalization-group equations of mixing matrices in a minimal extension of the Standard Model with isosinglet neutrinos.Comment: 31 pages, LaTeX, uses axodraw.st

Large-scale magnetic fields from inflation due to a CPTCPT-even Chern-Simons-like term with Kalb-Ramond and scalar fields

We investigate the generation of large-scale magnetic fields due to the breaking of the conformal invariance in the electromagnetic field through the $CPT$-even dimension-six Chern-Simons-like effective interaction with a fermion current by taking account of the dynamical Kalb-Ramond and scalar fields in inflationary cosmology. It is explicitly demonstrated that the magnetic fields on 1Mpc scale with the field strength of $\sim 10^{-9}$G at the present time can be induced.Comment: 18 pages, 6 figures, version accepted for publication in Eur. Phys. J.

International Influences and Drag: Just a Case of Tucking or Binding?

Recently there has been an  internationalisation in the training of UK drag performers. Whilst papers exist focused on drag kings and queens related to their community, few explore how kings/queens train – and fewer still explore international aspects. There are formal courses for drag, but historically this training was informal, present within specific performance communities built around LGBTQ cultures. Tracing dominant figures in such training – the drag mother/father – in order to historicise and contextualise the current explosion in drag performance,the paper argues that the potential globalisation of drag is largely down to the diversification of sources of knowledge available via the internet. Traditionally, performers trained with an established practitioner, where regional variances of drag were passed on. However, current new performers often learn ‘tricks of the trade’ through internet videos posted by people on other continents. In these videos, practitioners pass on their knowledge from the perspective of their locality, as if universal. New kings/queens are not passive in this training and locally infuse their acts, yet historical and local erasures persist. The paper argues that to engage with drag as performance one must be aware of locality and the deep connects drag has with its communities

Phase 1 study of the MDM2 inhibitor AMG 232 in patients with advanced P53 wild-type solid tumors or multiple myeloma

_Background_ This open-label, first-in-human, phase 1 study evaluated AMG 232, an oral selective MDM2 inhibitor in patients with TP53 wild-type (P53WT), advanced solid tumors or multiple myeloma (MM). _Methods_ In the dose escalation (n = 39), patients with P53WT refractory solid tumors enrolled to receive once-dailyAMG 232 (15, 30, 60, 120, 240, 480, and 960 mg) for seven days every 3 weeks (Q3W). In the dose expansion (n = 68), patients with MDM2-amplified (well-differentiated and dedifferentiated liposarcomas [WDLPS and DDLPS], glioblastoma multiforme [GBM], or other solid tumors [OST]), MDM2-overexpressing ER+ breast cancer (BC), or MM received AMG 232 at the maximum tolerated dose (MTD). Safety, pharmacokinetics, pharmacodynamics, and efficacy were assessed. _Results_ AMG 232 had acceptable safety up to up to 240 mg

Sociocultural considerations in aging men's health: implications and recommendations for the clinician

http://dx.doi.org/10.1016/j.jomh.2009.07.00