Membrane homeostasis beyond fluidity: control of membrane compressibility

Biomembranes are complex materials composed of lipids and proteins that compartmentalize biochemistry. They are actively remodeled in response to physical and metabolic cues, as well as during cell differentiation and stress. The concept of homeoviscous adaptation has become a textbook example of membrane responsiveness. Here, we discuss limitations and common misconceptions revolving around it. By highlighting key moments in the life cycle of a transmembrane protein, we illustrate that membrane thickness and a finely regulated membrane compressibility are crucial to facilitate proper membrane protein insertion, function, sorting, and inheritance. We propose that the unfolded protein response (UPR) provides a mechanism for endoplasmic reticulum (ER) membrane homeostasis by sensing aberrant transverse membrane stiffening and triggering adaptive responses that re-establish membrane compressibility

In Search of Homo Economicus: Behavioral Experiments in 15 Small-Scale Societies

We can summarize our results as follows. First, the canonical model is not supported in any society studied. Second, there is considerably more behavioral variability across groups than had been found in previous cross-cultural research, and the canonical model fails in a wider variety of ways than in previous experiments. Third, group-level differences in economic organization and the degree of market integration explain a substantial portion of the behavioral variation across societies: the higher the degree of market integration and the higher the payoffs to cooperation, the greater the level of cooperation in experimental games. Fourth, individual-level economic and demographic variables do not explain behavior either within or across groups. Fifth, behavior in the experiments is generally consistent with economic patterns of everyday life in these societies

Twenty-Four Hour Tonometry in Patients Suspected of Chronic Gastrointestinal Ischemia

Background and aims: Gastrointestinal tonometry is currently the only clinical diagnostic test that enables identification of symptomatic chronic gastrointestinal ischemia. Gastric exercise tonometry has proven its value for detection of ischemia in this patients group, but has its disadvantages. Earlier studies with postprandial tonometry gave unreliable results. In this study we challenged (again) the use of postprandial tonometry in patients suspected of gastrointestinal ischemia. Methods: Patients suspected for chronic gastrointestinal ischemia had standard diagnostic work up, including gastric exercise tonometry and 24-h tonometry using standard meals. Results: Thirty-three patients were enrolled in the study. Chronic gastrointestinal ischemia was diagnosed in 17 (52%) patients. The 24-h tonometry correctly predicted the presence of ischemia in 13/17 patients, and absence of ischemia in 15/16 patients. Conclusions: The use of 24-h tonometry after meals in patients suspected of gastrointestinal ischemia seems feasible, with promising accuracy for the detection of ischemia

Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands

Purpose: In June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland. Methods: Quarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti-inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression. Results: Overall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be amore limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (−0.42%, 95% CI, −0.66% to −0.18%), England (−0.09%, 95% CI, −0.11% to −0.08%), and Scotland (−0.67%, 95% CI, −0.79% to −0.55%); and falling trends in diclofenac initiation in the Netherlands (−0.03%, 95% CI, −0.06% to −0.01% per quarter) and Scotland (−0.04%, 95% CI, −0.05% to −0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation. Conclusions: The regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching

Abelian Higgs hair for extreme black holes and selection rules for snapping strings

It has been argued that a black hole horizon can support the long range fields of a Nielsen-Olesen string, and that one can think of such a vortex as black hole ``hair''. We show that the fields inside the vortex are completely expelled from a charged black hole in the extreme limit (but not in the near extreme limit). This would seem to imply that a vortex cannot be attached to an extreme black hole. Furthermore, we provide evidence that it is energetically unfavourable for a thin vortex to interact with a large extreme black hole. This dispels the notion that a black hole can support `long' Abelian Higgs hair in the extreme limit. We discuss the implications for strings that end at black holes, as in processes where a string snaps by nucleating black holes.Comment: 4 pages REVTeX plus 3 figures. Additional figures and mpeg movies available at http://www.damtp.cam.ac.uk/user/ats25/strhole.html This paper is a condensed version of gr-qc/9706004, and is essentially the talk presented at The Eighth Marcel Grossmann Meeting on General Relativity, 22-27 June 1997, The Hebrew University, Jerusalem, Israe

Evaluation of the Ability of LL-37 to Neutralise LPS In Vitro and Ex Vivo

BACKGROUND: Human cathelicidin LL-37 is a cationic antimicrobial peptide (AMP) which possesses a variety of activities including the ability to neutralise endotoxin. In this study, we investigated the role of LPS neutralisation in mediating LL-37's ability to inhibit Pseudomonas aeruginosa LPS signalling in human monocytic cells. METHODOLOGY/PRINCIPAL FINDINGS: Pre-treatment of monocytes with LL-37 significantly inhibited LPS-induced IL-8 production and the signalling pathway of associated transcription factors such as NF-κB. However, upon removal of LL-37 from the media prior to LPS stimulation, these inhibitory effects were abolished. These findings suggest that the ability of LL-37 to inhibit LPS signalling is largely dependent on extracellular LPS neutralisation. In addition, LL-37 potently inhibited cytokine production induced by LPS extracted from P. aeruginosa isolated from the lungs of cystic fibrosis (CF) patients. In the CF lung, polyanionic molecules such as glycosaminoglycans (GAGs) and DNA bind LL-37 and impact negatively on its antibacterial activity. In order to determine whether such interactions interfere with the LPS neutralising ability of LL-37, the status of LL-37 and its ability to bind LPS in CF sputum were investigated. Overall our findings suggest that in the CF lung, the ability of LL-37 to bind LPS and inhibit LPS-induced IL-8 production is attenuated as a result of binding to DNA and GAGs. However, LL-37 levels and its concomitant LPS-binding activity can be increased with a combination of DNase and GAG lyase (heparinase II) treatment. CONCLUSIONS/SIGNIFICANCE: Overall, these findings suggest that a deficiency in available LL-37 in the CF lung may contribute to greater LPS-induced inflammation during CF lung disease

What is the role of public feeder markets in developing technology-based small firms? An exploration of the motivations for listing on AIM since the GFC

In the aftermath of the 2007 global financial crisis (GFC) stock markets experienced sharp decline in listings and marked reduction in Initial Public Offerings (IPOs). This paper explores the factors determining UK technology based small firm (TBSF) listings on the UK Alternative Investment Market (AIM) and whether this market has a role to play in their future development. A case study approach is used to contrast the experiences of five recent AIM listed TBSFs with five TBSFs approaching private equity investment exit that are considering an IPO. The paper concludes that macro market conditions, rather than managerial resource base or AIM market structural factors were most influential in TBSF pecking order preferences to undertake IPOs. From a resource based management perspective lifelong entrepreneurs were more likely than serial entrepreneurs to favour an IPO exit, as it supported their aims to continue to manage and grow UK-based companies. Additionally, with a more buoyant and sustainable AIM market TBSF investors are more likely to choose IPOs. To conclude, AIM played an important role in listed UK TBSF development. A more buoyant AIM could ease the UK finance escalator’s flow, facilitating more rapid UK TBSF growth

Double-well magnetic trap for Bose-Einstein condensates

We present a magnetic trapping scheme for neutral atoms based on a hybrid of Ioffe-Pritchard and Time-averaged Orbiting Potential traps. The resulting double-well magnetic potential has readily controllable barrier height and well separation. This offers a new tool for studying the behavior of Bose condensates in double-well potentials, including atom interferometry and Josephson tunneling. We formulate a description for the potential of this magnetic trap and discuss practical issues such as loading with atoms, evaporative cooling and manipulating the potential.Comment: 7 pages, 6 figures, Revtex

Risk Tolerance, Self-Interest, and Social Preferences

We use an experimental method to investigate whether systematic relationships exist across distinct aspects of individual preferences: risk aversion in monetary outcomes, altruism in a twoperson context, and social preferences in a larger group context. Individual preferences across these three contexts are measured, and there is no possibility for risk sharing, wealth effects, or updating expectations of the population choices. We find that social preferences are related to demographic variables, including years of education, gender, and age. Perhaps most importantly, self allocation in a two-person dictator game is related to social preferences in a group context. Participants who are more generous in a dictator game are more likely to vote against their selfinterest in a group decision-making task which we interpret to be expressions of social preferences