Simulations of a lattice model of two-headed linear amphiphiles: influence of amphiphile asymmetry

Using a 2D lattice model, we conduct Monte Carlo simulations of micellar aggregation of linear-chain amphiphiles having two solvophilic head groups. In the context of this simple model, we quantify how the amphiphile architecture influences the critical micelle concentration (CMC), with a particular focus on the role of the asymmetry of the amphiphile structure. Accordingly, we study all possible arrangements of the head groups along amphiphile chains of fixed length $N=12$ and 16 molecular units. This set of idealized amphiphile architectures approximates many cases of symmetric and asymmetric gemini surfactants, double-headed surfactants and boloform surfactants. Consistent with earlier results, we find that the number of spacer units $s$ separating the heads has a significant influence on the CMC, with the CMC increasing with $s$ for $s<N/2$. In comparison, the influence of the asymmetry of the chain architecture on the CMC is much weaker, as is also found experimentally.Comment: 30 pages, 17 fgure

STS-99 Shuttle Radar Topography Mission Stability and Control

The Shuttle Radar Topography Mission (SRTM) flew aboard Space Shuttle Endeavor February 2000 and used interferometry to map 80% of the Earth's landmass. SRTM employed a 200-foot deployable mast structure to extend a second antenna away from the main antenna located in the Shuttle payload bay. Mapping requirements demanded precision pointing and orbital trajectories from the Shuttle on-orbit Flight Control System (PCS). Mast structural dynamics interaction with the FCS impacted stability and performance of the autopilot for attitude maneuvers and pointing during mapping operations. A damper system added to ensure that mast tip motion remained with in the limits of the outboard antenna tracking system while mapping also helped to mitigate structural dynamic interaction with the FCS autopilot. Late changes made to the payload damper system, which actually failed on-orbit, required a redesign and verification of the FCS autopilot filtering schemes necessary to ensure rotational control stability. In-flight measurements using three sensors were used to validate models and gauge the accuracy and robustness of the pre-mission notch filter design

Comparing leakage currents and dark count rates in Geiger-mode avalanche photodiodes

This letter presents an experimental study of dark count rates and leakage current in Geiger-mode avalanche photodiodes (GM APD). Experimental results from circular diodes over a range of areas (20-500 mum diam), exhibit leakage current levels orders of magnitude higher than anticipated from dark count rates. Measurements of the area and peripheral components of the leakage current indicate that the majority of the current in reverse bias does not enter the high-field region of the diode, and therefore, does not contribute to the dark count rate. Extraction of the area leakage current term from large-area devices (500 mum) corresponds well with the measured dark count rates on smaller devices (20 mum). Finally, the work indicates how dark count measurements represent 10(-18) A levels of leakage current detection in GM APDs. (C) 2002 American Institute of Physics. (DOI: 10.1063/1.1483119

Assessing and Manipulating The Illusion of Control of Video Poker Players

The present investigation explored the presence of illusory control in recreation-al video poker players. Using a multi-monitor computer which allowed for two different types of games to be presented concurrently, one on each monitor, players were allowed to freely choose which game they wished to play. One option allowed for the player to select the cards they wished to hold and discard, while the other option was designed such that the computer automatically se-lected the most probabilistically optimal sequence of cards to hold and discard. In the first experiment, two groups of ten participants were exposed to one of two rules (accurate or inaccurate) regarding the chances of winning. No differ-ences in response allocations between the games were found. In the second experiment, thirteen participants were sequentially exposed to a non-rule base-line followed by an inaccurate and subsequently accurate rule. Twelve of the thirteen players preferred the self-selecting game, and following the introduction of an experimenter given rule that was designed to strengthen the illusion (i.e., that the self-selecting option was better), most players increased their preference for this option. However, following the introduction of an experimenter given rule that attempted to weaken the illusion, only about half the participants fol-lowed that rule and reduced playing the self-selecting option. Variability across participants was able to be explained by examining each player’s verbal talk which was emitted overtly throughout the duration of the experiment. Implica-tions for understanding the illusion of control and the verbal behavior of gam-blers are presented

Statin use and risk of community acquired pneumonia in older people: population based case-control study

Objective To test the hypothesis that hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) may decrease the risk of community acquired pneumonia

A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis.

ObjectiveEtrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.DesignIn the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).ResultsIn the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.ConclusionEtrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted

A Search for Exozodiacal Clouds with Kepler

Planets embedded within dust disks may drive the formation of large scale clumpy dust structures by trapping dust into resonant orbits. Detection and subsequent modeling of the dust structures would help constrain the mass and orbit of the planet and the disk architecture, give clues to the history of the planetary system, and provide a statistical estimate of disk asymmetry for future exoEarth-imaging missions. Here we present the first search for these resonant structures in the inner regions of planetary systems by analyzing the light curves of hot Jupiter planetary candidates identified by the Kepler mission. We detect only one candidate disk structure associated with KOI 838.01 at the 3-sigma confidence level, but subsequent radial velocity measurements reveal that KOI 838.01 is a grazing eclipsing binary and the candidate disk structure is a false positive. Using our null result, we place an upper limit on the frequency of dense exozodi structures created by hot Jupiters. We find that at the 90% confidence level, less than 21% of Kepler hot Jupiters create resonant dust clumps that lead and trail the planet by ~90 degrees with optical depths >~5*10^-6, which corresponds to the resonant structure expected for a lone hot Jupiter perturbing a dynamically cold dust disk 50 times as dense as the zodiacal cloud.Comment: 22 pages, 6 figures, Accepted for publication in Ap

An integrated approach to historical population assessment of the great whales: case of the New Zealand southern right whale

Accurate estimation of historical abundance provides an essential baseline for judging the recovery of the great whales. This is particularly challenging for whales hunted prior to twentieth century modern whaling, as population-level catch records are often incomplete. Assessments of whale recovery using pre-modern exploitation indices are therefore rare, despite the intensive, global nature of nineteenth century whaling. Right whales (Eubalaena spp.) were particularly exploited: slow swimmers with strong fidelity to sheltered calving bays, the species made predictable and easy targets. Here, we present the first integrated population-level assessment of the whaling impact and pre-exploitation abundance of a right whale, the New Zealand southern right whale (E. australis). In this assessment, we use a Bayesian population dynamics model integrating multiple data sources: nineteenth century catches, genetic constraints on bottleneck size and individual sightings histories informing abundance and trend. Different catch allocation scenarios are explored to account for uncertainty in the population's offshore distribution. From a pre-exploitation abundance of 28 800–47 100 whales, nineteenth century hunting reduced the population to approximately 30–40 mature females between 1914 and 1926. Today, it stands at less than 12% of pre-exploitation abundance. Despite the challenges of reconstructing historical catches and population boundaries, conservation efforts of historically exploited species benefit from targets for ecological restoration

Pro-survival redox signalling in progesterone-mediated retinal neuroprotection

Retinitis pigmentosa (RP) is a group of hereditary retinal diseases, characterised by photoreceptor cell loss. Despite a substantial understanding of the mechanisms leading to cell death, an effective therapeutic strategy is sought. Our laboratory has previously demonstrated the neuroprotective properties of Norgestrel, a progesterone analogue, in the degenerating retina, mediated in part by the neurotrophic factor basic fibroblast growth factor (bFGF). In other retinal studies, we have also presented a pro-survival role for reactive oxygen species (ROS), downstream of bFGF. Thus, we hypothesized that Norgestrel utilises bFGF-driven ROS production to promote photoreceptor survival. Using the 661W photoreceptor-like cell line, we now show that Norgestrel, working through progesterone receptor membrane complex 1 (PGRMC1); generates an early burst of pro-survival bFGF-induced ROS. Using the rd10 mouse model of RP, we confirm that Norgestrel induces a similar early pro-survival increase in retinal ROS. Norgestrel-driven protection in the rd10 retina was attenuated in the presence of antioxidants. This study therefore presents an essential role for ROS signalling in Norgestrel-mediated neuroprotection in vitro and demonstrates that Norgestrel employs a similar pro-survival mechanism in the degenerating retina

Progesterone analogue protects stressed photoreceptors via bFGF-mediated calcium influx.

Retinitis pigmentosa (RP) is a degenerative retinal disease leading to photoreceptor cell loss. In 2011, our group identified the synthetic progesterone ‘Norgestrel’ as a potential treatment for RP. Subsequent research showed Norgestrel to work through progesterone receptor membrane component 1 (PGRMC1) activation and upregulation of neuroprotective basic fibroblast growth factor (bFGF). Using trophic factor deprivation of 661W photoreceptor-like cells, we aimed to further elucidate the mechanism leading to Norgestrel-induced neuroprotection. In the present manuscript, we show by flow cytometry and live-cell immunofluorescence that Norgestrel induces an increase in cytosolic calcium in both healthy and stressed 661Ws over 24h. Specific PGRMC1 inhibition by AG205 (1 μM) showed this rise to be PGRMC1-dependent, primarily utilising calcium from extracellular sources, for blockade of L-type calcium channels by verapamil (50 μM) prevented a Norgestrel-induced calcium influx in stressed cells. Calcium influx was also shown to be bFGF-dependent, for siRNA knock down of bFGF prevented Norgestrel-PGRMC1 induced changes in cytosolic calcium. Notably, we demonstrate PGRMC1-activation is necessary for Norgestrel-induced bFGF upregulation. We propose that Norgestrel protects through the following pathway: binding to and activating PGRMC1 expressed on the surface of photoreceptor cells, PGRMC1 activation drives bFGF upregulation and subsequent calcium influx. Importantly, raised intracellular calcium is critical to Norgestrel's protective efficacy, for extracellular calcium chelation by EGTA abrogates the protective effects of Norgestrel on stressed 661W cells in vitro