Imaging Deformed Proteins: Characterising the State Fully

By analysing the positions of individual unit cells in the image of a distorted macromolecular crystal, it is possible to achieve considerably more than is achieved by the correlation averaging or unbending now widely practised. It is possible partly to compensate for individual molecular distortion; and it is possible to identify molecules in equivalent environments (which can be expected to be in equivalent states of strain), selective averaging of which yields images that show how strain is accommodated at the sub-molecular level. The possible presence of surface forces applied to the crystal by its support film complicates the analysis and adds two additional parameters, not previously identified, to those necessary to characterise the environment of each molecule fully; these surface stress parameters can be estimated on the basis of a simple (isotropic) model of the elastic behaviour of a 2-D crystal. The appropriate mathematical description of strain and elasticity in 2-D crystals has been assembled concisely, and a set of new procedures developed allowing their practical exploitation within the Semper image processing system

Interactive Image Processing for Electron Microscopy: Matching Hardware with Software

The image processing techniques used \u27a posteriori\u27 to extract information from electron micrographs are surveyed, including particularly image averaging, selective averaging, 3-D reconstruction, and high resolution focal series restoration; recent developments in online image pick up and control have led to fully automatic focussing, stigmating and alignment by a frame store system equipped with a real time correlator board. The diversity of the techniques encountered calls for large integrated program systems with flexible command languages; however, a dilemma exists between providing the user with convenient control of special hardware facilities such as frame stores and array processors, and preventing the programs from becoming so specific that they are extremely short lived. Some of the compromises made in the Semper system are noted

A family tree of Markov models in systems biology

Motivated by applications in systems biology, we seek a probabilistic framework based on Markov processes to represent intracellular processes. We review the formal relationships between different stochastic models referred to in the systems biology literature. As part of this review, we present a novel derivation of the differential Chapman-Kolmogorov equation for a general multidimensional Markov process made up of both continuous and jump processes. We start with the definition of a time-derivative for a probability density but place no restrictions on the probability distribution, in particular, we do not assume it to be confined to a region that has a surface (on which the probability is zero). In our derivation, the master equation gives the jump part of the Markov process while the Fokker-Planck equation gives the continuous part. We thereby sketch a {}``family tree'' for stochastic models in systems biology, providing explicit derivations of their formal relationship and clarifying assumptions involved.Comment: 18 pages, 2 figure

Probing microscopic origins of confined subdiffusion by first-passage observables

Subdiffusive motion of tracer particles in complex crowded environments, such as biological cells, has been shown to be widepsread. This deviation from brownian motion is usually characterized by a sublinear time dependence of the mean square displacement (MSD). However, subdiffusive behavior can stem from different microscopic scenarios, which can not be identified solely by the MSD data. In this paper we present a theoretical framework which permits to calculate analytically first-passage observables (mean first-passage times, splitting probabilities and occupation times distributions) in disordered media in any dimensions. This analysis is applied to two representative microscopic models of subdiffusion: continuous-time random walks with heavy tailed waiting times, and diffusion on fractals. Our results show that first-passage observables provide tools to unambiguously discriminate between the two possible microscopic scenarios of subdiffusion. Moreover we suggest experiments based on first-passage observables which could help in determining the origin of subdiffusion in complex media such as living cells, and discuss the implications of anomalous transport to reaction kinetics in cells.Comment: 21 pages, 3 figures. Submitted versio

TYC 8380-1953-1: Discovery of an RS CVn binary through the XMM-Newton slew survey

In this paper we report the discovery of the chromospherically active (RS CVn type) binary TYC 8380-1953-1 through the XMM-Newton slew survey and present results of our optical and X-ray follow-up. With a flux limit of $6 \times 10^{-13}$ erg cm$^{-2}$ s$^{-1}$ in the soft band ($0.2 - 2$ keV), the XMM-Newton slew has a similar sensitivity to the ROSAT All Sky Survey allowing interesting sources to be identified by their long-term variability. Two different types of stellar sources are detected in shallow X-ray surveys: young stars (both pre-main and main sequence stars) and chromospherically active binaries (BY Dra and RS CVn type systems). The discovery of stars in such surveys and the study of their nature through optical follow-ups is valuable to determine their spatial distribution and scale height in the Galaxy. Our analysis shows that TYC 8380-1953-1 is a double-lined spectroscopic binary with both components having similar spectral type (likely K0/2+K3/5) and luminosity. With a typical coronal temperature for an RS CVn system ($kT \sim 1.15$ keV) and an X-ray luminosity in the $0.3-10$ keV energy band higher than $4 \times 10^{31}$ erg\,s$^{-1}$, TYC 8380-1953-1 lies among the most X-ray luminous RS CVn binaries.Comment: Accepted for publication in the PASP. 18 pages, 10 figure

Geometry-controlled kinetics

It has long been appreciated that transport properties can control reaction kinetics. This effect can be characterized by the time it takes a diffusing molecule to reach a target -- the first-passage time (FPT). Although essential to quantify the kinetics of reactions on all time scales, determining the FPT distribution was deemed so far intractable. Here, we calculate analytically this FPT distribution and show that transport processes as various as regular diffusion, anomalous diffusion, diffusion in disordered media and in fractals fall into the same universality classes. Beyond this theoretical aspect, this result changes the views on standard reaction kinetics. More precisely, we argue that geometry can become a key parameter so far ignored in this context, and introduce the concept of "geometry-controlled kinetics". These findings could help understand the crucial role of spatial organization of genes in transcription kinetics, and more generally the impact of geometry on diffusion-limited reactions.Comment: Submitted versio

Dynamics and Scaling of 2D Polymers in a Dilute Solution

The breakdown of dynamical scaling for a dilute polymer solution in 2D has been suggested by Shannon and Choy [Phys. Rev. Lett. {\bf 79}, 1455 (1997)]. However, we show here both numerically and analytically that dynamical scaling holds when the finite-size dependence of the relevant dynamical quantities is properly taken into account. We carry out large-scale simulations in 2D for a polymer chain in a good solvent with full hydrodynamic interactions to verify dynamical scaling. This is achieved by novel mesoscopic simulation techniques

Anomalous ion diffusion within skeletal muscle transverse tubule networks

<p>Abstract</p> <p>Background</p> <p>Skeletal muscle fibres contain transverse tubular (t-tubule) networks that allow electrical signals to rapidly propagate into the fibre. These electrical signals are generated by the transport of ions across the t-tubule membranes and this can result in significant changes in ion concentrations within the t-tubules during muscle excitation. During periods of repeated high-frequency activation of skeletal muscle the t-tubule K⁺concentration is believed to increase significantly and diffusive K⁺transport from the t-tubules into the interstitial space provides a mechanism for alleviating muscle membrane depolarization. However, the tortuous nature of the highly branched space-filling t-tubule network impedes the diffusion of material through the network. The effective diffusion coefficient for ions in the t-tubules has been measured to be approximately five times lower than in free solution, which is significantly different from existing theoretical values of the effective diffusion coefficient that range from 2–3 times lower than in free solution. To resolve this discrepancy, in this paper we study the process of diffusion within electron microscope scanned sections of the skeletal muscle t-tubule network using mathematical modelling and computer simulation techniques. Our model includes t-tubule geometry, tautness, hydrodynamic and non-planar network factors.</p> <p>Results</p> <p>Using our model we found that the t-tubule network geometry reduced the K⁺diffusion coefficient to 19–27% of its value in free solution, which is consistent with the experimentally observed value of 21% and is significantly smaller than existing theoretical values that range from 32–50%. We also found that diffusion in the t-tubules is anomalous for skeletal muscle fibres with a diameter of less than approximately 10–20 μm as a result of obstructed diffusion. We also observed that the [K⁺] within the interior of the t-tubule network during high-frequency activation is greater for fibres with a larger diameter. Smaller skeletal muscle fibres are therefore more resistant to membrane depolarization. Because the t-tubule network is anisotropic and inhomogeneous, we also found that the [K⁺] distribution generated within the network was irregular for fibres of small diameter.</p> <p>Conclusion</p> <p>Our model explains the measured effective diffusion coefficient for ions in skeletal muscle t-tubules.</p

Observation of Parity Nonconservation in Moller Scattering

We report a measurement of the parity-violating asymmetry in fixed target electron-electron (Moller) scattering: A_PV = -175 +/- 30 (stat.) +/- 20 (syst.) parts per billion. This first direct observation of parity nonconservation in Moller scattering leads to a measurement of the electron's weak charge at low energy Q^e_W = -0.053 +/- 0.011. This is consistent with the Standard Model expectation at the current level of precision: sin^2\theta_W(M_Z)_MSbar = 0.2293 +/- 0.0024 (stat.) +/- 0.0016 (syst.) +/- 0.0006 (theory).Comment: Version 3 is the same as version 2. These versions contain minor text changes from referee comments and a change in the extracted value of Q^e_W and sin^2\theta_W due to a change in the theoretical calculation of the bremsstrahulung correction (ref. 16