Structural basis of complement membrane attack complex formation

In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a ‘multi-hit’ mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a ‘split-washer’ configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular β-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration

Ground-based photometry of the 21-day Neptune HD106315c

Space-based transit surveys such as K2 and TESS allow the detection of small transiting planets with orbital periods beyond 10 days. Few of these warm Neptunes are currently known around stars bright enough to allow for detailed follow-up observations dedicated to their atmospheric characterization. The 21-day period and 3.95 $R_\oplus$ planet HD106315c has been discovered based on the observation of two of its transits by K2. We have observed HD106315 using the 1.2m Euler telescope equipped with the EulerCam camera on two instances to confirm the transit using broad band photometry and refine the planetary period. Based on two observed transits of HD106315c, we detect its $\sim$1 mmag transit and obtain a precise measurement of the planetary ephemerids, which are critical for planning further follow-up observations. We have used the attained precision together with the predicted yield from the TESS mission to evaluate the potential for ground-based confirmation of Neptune-sized planets found by TESS. We find that 1-meter-class telescopes on the ground equipped with precise photometers could substantially contribute to the follow-up of 162 TESS candidates orbiting stars with magnitudes of $V \leq 14$. Out of these, 74 planets orbit stars with $V \leq 12$ and 12 planets orbit $V \leq 10$, which makes these candidates high-priority objects for atmospheric characterization with high-end instrumentation.Comment: Published in A&A letters, 4 pages, 3 figure

Conditional sampling for barrier option pricing under the LT method

We develop a conditional sampling scheme for pricing knock-out barrier options under the Linear Transformations (LT) algorithm from Imai and Tan (2006). We compare our new method to an existing conditional Monte Carlo scheme from Glasserman and Staum (2001), and show that a substantial variance reduction is achieved. We extend the method to allow pricing knock-in barrier options and introduce a root-finding method to obtain a further variance reduction. The effectiveness of the new method is supported by numerical results

Radiation reaction on charged particles in three-dimensional motion in classical and quantum electrodynamics

We extend our previous work (see arXiv:quant-ph/0501026), which compared the predictions of quantum electrodynamics concerning radiation reaction with those of the Abraham-Lorentz-Dirac theory for a charged particle in linear motion. Specifically, we calculate the predictions for the change in position of a charged scalar particle, moving in three-dimensional space, due to the effect of radiation reaction in the one-photon-emission process in quantum electrodynamics. The scalar particle is assumed to be accelerated for a finite period of time by a three-dimensional electromagnetic potential dependent only on one of the spacetime coordinates. We perform this calculation in the $\hbar\to 0$ limit and show that the change in position agrees with that obtained in classical electrodynamics with the Lorentz-Dirac force treated as a perturbation. We also show for a time-dependent but space-independent electromagnetic potential that the forward-scattering amplitude at order $e^2$ does not contribute to the position change in the $\hbar \to 0$ limit after the mass renormalization is taken into account.Comment: Latex, 20page

Sub-shot-noise shadow sensing with quantum correlations

The quantised nature of the electromagnetic field sets the classical limit to the sensitivity of position measurements. However, techniques based on the properties of quantum states can be exploited to accurately measure the relative displacement of a physical object beyond this classical limit. In this work, we use a simple scheme based on the split-detection of quantum correlations to measure the position of a shadow at the single-photon light level, with a precision that exceeds the shot-noise limit. This result is obtained by analysing the correlated signals of bi-photon pairs, created in parametric downconversion and detected by an electron multiplying CCD (EMCCD) camera employed as a split-detector. By comparing the measured statistics of spatially anticorrelated and uncorrelated photons we were able to observe a significant noise reduction corresponding to an improvement in position sensitivity of up to 17% (0.8dB). Our straightforward approach to sub-shot-noise position measurement is compatible with conventional shadow-sensing techniques based on the split-detection of light-fields, and yields an improvement that scales favourably with the detector’s quantum efficiency

DESIGN OF COX-2 INHIBITORS-AN IN-SILICO APPROACH

Objective: The aim of the present work was to design the novel series of chalcone derivatives of indane-1,3-dione for its inhibition towards COX-2. Methods: COX-2 inhibitors were designed on the binding ability of the compounds with the target. Docking analysis was performed using Acclerys discovery studio 3.5. Molecular properties, ADME parameters, Toxicity parameters were analysed using the same in-silico tool. Results: Most of the designed compounds were possessing good binding affinity towards the COX-2. Other in-silico parameters such as ADMET and TOPKAT were within the appreciable range. Among all the designed compounds several compounds possess good CDOCKER energy and CDOCKER interaction energy with specific amino acid indicating that it could possess good binding with the target. Most of the design compounds could act as COX-2 because it forms hydrogen bonding with ARG120. Conclusion: Compound l possess good binding affinity indicating that the presence of hydroxyl group in the phenyl ring possess good activity which can be further optimized for its druggabality after its pharmacological activity. Â&nbsp

The dynamism of salt crust patterns on playas

Playas are common in arid environments and can be major sources of mineral dust that can influence global climate. These landforms typically form crusts that limit evaporation and dust emission, modify surface erosivity and erodibility, and can lead to over prediction or under prediction of (1) dust-emission potential and (2) water and heat fluxes in energy balance modeling. Through terrestrial laser scanning measurements of part of the Makgadikgadi Pans of Botswana (a Southern Hemisphere playa that emits significant amounts of dust), we show that over weeks, months, and a year, the shapes of these surfaces change considerably (ridge thrusting of >30 mm/week) and can switch among continuous, ridged, and degraded patterns. Ridged pattern development changes the measured aerodynamic roughness of the surface (as much as 3 mm/week). The dynamic nature of these crusted surfaces must be accounted for in dust entrainment and moisture balance formulae to improve regional and global climate models

IgG anti-apolipoprotein A-1 antibodies in patients with systemic lupus erythematosus are associated with disease activity and corticosteroid therapy: an observational study.

IgG anti-apolipoprotein A-1 (IgG anti-apoA-1) antibodies are present in patients with systemic lupus erythematosus (SLE) and may link inflammatory disease activity and the increased risk of developing atherosclerosis and cardiovascular disease (CVD) in these patients. We carried out a rigorous analysis of the associations between IgG anti-apoA-1 levels and disease activity, drug therapy, serology, damage, mortality and CVD events in a large British SLE cohort