Jump rates for surface diffusion of large molecules from first principles.

We apply a recently developed stochastic model for the surface diffusion of large molecules to calculate jump rates for 9,10-dithioanthracene on a Cu(111) surface. The necessary input parameters for the stochastic model are calculated from first principles using density functional theory (DFT). We find that the inclusion of van der Waals corrections to the DFT energies is critical to obtain good agreement with experimental results for the adsorption geometry and energy barrier for diffusion. The predictions for jump rates in our model are in excellent agreement with measured values and show a marked improvement over transition state theory (TST). We find that the jump rate prefactor is reduced by an order of magnitude from the TST estimate due to frictional damping resulting from energy exchange with surface phonons, as well as a rotational mode of the diffusing molecule.

Stochastic models for surface diffusion of molecules.

We derive a stochastic model for the surface diffusion of molecules, starting from the classical equations of motion for an N-atom molecule on a surface. The equation of motion becomes a generalized Langevin equation for the center of mass of the molecule, with a non-Markovian friction kernel. In the Markov approximation, a standard Langevin equation is recovered, and the effect of the molecular vibrations on the diffusion is seen to lead to an increase in the friction for center of mass motion. This effective friction has a simple form that depends on the curvature of the lowest energy diffusion path in the 3N-dimensional coordinate space. We also find that so long as the intramolecular forces are sufficiently strong, memory effects are usually not significant and the Markov approximation can be employed, resulting in a simple one-dimensional model that can account for the effect of the dynamics of the molecular vibrations on the diffusive motion.

Tomography by point source digital holographic microscopy.

We propose a tomographic method for point source inline holographic microscopy. By recording a set of holograms at different illumination angles, shadowing effects are eliminated resulting in three-dimensional images with the same precision at the micrometer-scale in all directions. The advantage of our tomographic approach is that it works for both absorbing and phase objects, regardless of the change of refractive index at interfaces. We develop the method with computer simulations and demonstrate its strength by presenting experimental results for micrometer-sized polystyrene beads and a cotton fiber.

A three-state model with loop entropy for the overstretching transition of DNA.

We introduce a three-state model for a single DNA chain under tension that distinguishes among B-DNA, S-DNA, and M (molten or denatured) segments and at the same time correctly accounts for the entropy of molten loops, characterized by the exponent c in the asymptotic expression S approximately -c ln n for the entropy of a loop of length n. Force extension curves are derived exactly by employing a generalized Poland-Scheraga approach and then compared to experimental data. Simultaneous fitting to force-extension data at room temperature and to the denaturation phase transition at zero force is possible and allows us to establish a global phase diagram in the force-temperature plane. Under a stretching force, the effects of the stacking energy (entering as a domain-wall energy between paired and unpaired bases) and the loop entropy are separated. Therefore, we can estimate the loop exponent c independently from the precise value of the stacking energy. The fitted value for c is small, suggesting that nicks dominate the experimental force extension traces of natural DNA.

Packed domain Rayleigh-Sommerfeld wavefield propagation for large targets.

For applications in the domain of digital holographic microscopy, we present a fast algorithm to propagate scalar wave fields from a small source area to an extended, parallel target area of coarser sampling pitch, using the first Rayleigh-Sommerfeld diffraction formula. Our algorithm can take full advantage of the fast Fourier transform by decomposing the convolution kernel of the propagation into several convolution kernel patches. Using partial overlapping of the patches together with a soft blending function, the Fourier spectrum of these patches can be reduced to a low number of significant components, which can be stored in a compact sparse array structure. This allows for rapid evaluation of the partial convolution results by skipping over negligible components through the Fourier domain pointwise multiplication and direct mapping of the remaining multiplication results into a Fourier domain representation of the coarsly sampled target patch. The algorithm has been verified experimentally at a numerical aperture of 0.62, not showing any significant resolution limitations.

The role of "inert" surface chemistry in marine biofouling prevention.

The settlement and colonization of marine organisms on submerged man-made surfaces is a major economic problem for many marine industries. The most apparent detrimental effects of biofouling are increased fuel consumption of ships, clogging of membranes and heat exchangers, disabled underwater sensors, and growth of biofoulers in aquaculture systems. The presently common-but environmentally very problematic-way to deal with marine biofouling is to incorporate biocides, which use biocidal products in the surface coatings to kill the colonizing organisms, into the surface coatings. Since the implementation of the International Maritime Organization Treaty on biocides in 2008, the use of tributyltin (TBT) is restricted and thus environmentally benign but effective surface coatings are required. In this short review, we summarize the different strategies which are pursued in academia and industry to better understand the mechanisms of biofouling and to develop strategies which can be used for industrial products. Our focus will be on chemically "inert" model surface coatings, in particular oligo- and poly(ethylene glycol) (OEG and PEG) functionalized surface films. The reasons for choosing this class of chemistry as an example are three-fold: Firstly, experiments on spore settlement on OEG and PEG coatings help to understand the mechanism of non-fouling of highly hydrated interfaces; secondly, these studies defy the common assumption that surface hydrophilicity-as measured by water contact angles-is an unambiguous and predictive tool to determine the fouling behavior on the surface; and thirdly, choosing this system is a good example for "interfacial systems chemistry": it connects the behavior of unicellular marine organisms with the antifouling properties of a hydrated surface coating with structural and electronic properties as derived from ab initio quantum mechanical calculations using the electronic wave functions of oxygen, hydrogen, and carbon. This short review is written to outline for non-experts the hierarchical structure in length- and timescale of marine biofouling and the role of surface chemistry in fouling prevention. Experts in the field are referred to more specialized recent reviews.

Stretching and unfolding of multidomain biopolymers: a statistical mechanics theory of titin.

Single-molecule manipulation has allowed the forced unfolding of multidomain proteins. Here we develop a theory that not only explains these experiments, but also points out a number of difficulties in their interpretation and makes suggestions for further experiments. Our theory is valid for essentially any molecule that can be unfolded in the AFM: as an example we present force-extension curves for the unfolding of both titin and RNA hairpins. For titin we reproduce force-extension curves, the dependence of break force on pulling speed, and break-force distributions, and also validate two common experimental views: unfolding titin Ig domains can be explained as stepwise increases in contour length, and increasing force peaks in native Ig sequences represent a hierarchy of bond strengths.

Dynamics of single-molecule force-ramp experiments: The role of fluctuations.

In the force-ramp mode of the atomic force microscope, the force with which a macromolecule is stretched is increased linearly in time by properly controlling the motion of the cantilever through a feedback loop. Using a master equation approach for the coupled cantilever-macromolecule system, we mimic such a feedback loop, to study nonequilibrium effects in the measurements of force-extension curves and fluctuations. In particular, it is shown that the fluctuations are the same for force-ramp experiments and for the more commonly used constant velocity experiments. Thus the exact same statistics suffice for the explanation of either experiment. Specific results are presented for the stretching of Dextran.

Quantitative phase measurements of tendon collagen fibres.

Collagen is the main component of structural mammalian tissues. In tendons, collagen is arranged into fibrils with diameters ranging from 30 nm to 500 nm. These fibrils are further assembled into fibres several micrometers in diameter. Upon excessive thermal or mechanical stress, damage may occur in tendons at all levels of the structural hierarchy. At the fibril level, reported damage includes swelling and the appearance of discrete sites of plastic deformation that are best observed at the nanometer-scale using, for example, scanning electron microscopy. In this paper, digital in-line holographic microscopy is used for quantitative phase imaging to measure both the refractive index and diameter of collagen fibres in a water suspension in the native state, after thermal treatments, and after mechanical overload. Fibres extracted from tendons and subsequently exposed to 70 °C for 5, 15, or 30 minutes show a significant decrease in refractive index and an increase in diameter. A significant increase in refractive index is also observed for fibres extracted from tendons that were subjected to five tensile overload cycles.

Breaking bonds in the atomic force microscope: theory and analysis.

A theoretical framework is developed to analyze molecular bond breaking in dynamic force spectroscopy using atomic force microscopy. An analytic expression of the observed bond breaking probability as a function of force is obtained in terms of the relevant physical parameters. The force-ramp mode is discussed in detail, which gives the best framework to extract the relevant physical parameters such as the potential depth and its width, if a set of widely different force-loading rates are used. We also show that the commonly used Ritchie-Evans model is incomplete and that it is only applicable for forces well below the maximum permitted by the potential. Statistical complications arising from the use of constant velocity experiments are discussed in detail.

Nonequilibrium theory of polymer stretching based on the master equation.

We present a model for fast polymer-stretching experiments. We use the master equation and argue that the end-to-end extension of a polymer molecule can be used as a stochastic variable after appropriate coarse graining. The main effect of increasing pulling speed or force loading rate is a marked hysteresis in the force-extension curve as well as an overall shift of the curve to higher forces when compared to the equilibrium curve. This can be understood in terms of the moments of the transition probability in the master equation. An analysis of the fluctuations and relaxation times is also given in the framework of our theory.

Graphical methods for the analysis of shear-induced detachment of cells and microorganisms.

Treating shear stress induced detachment of micro-organisms as a bond breaking mechanism, the authors present three intuitive graphical approaches to determine the relevant parameters in the Arrhenius rate equation, i.e., attachment energy, prefactor, and maximum shear stress. They demonstrate the methods with the detachment of polystyrene spheres and show that having three different methods presents the opportunity to check the consistency of the results.

Thrombolysis and clinical outcome in patients with stroke after implementation of the Tyrol Stroke Pathway: a retrospective observational study.

BACKGROUND: Intravenous thrombolysis for ischaemic stroke remains underused worldwide. We aimed to assess whether our statewide comprehensive stroke management programme would improve thrombolysis use and clinical outcome in patients. METHODS: In 2008-09, we designed the Tyrol Stroke Pathway, which provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation. It was commenced in Tyrol, Austria, as a long-term routine-care programme and aimed to include all patients with stroke in the survey area. We focused on thrombolysis use and outcome in the first full 4 years of implementation (2010-13). FINDINGS: We enrolled 4947 (99%) of 4992 patients with ischaemic stroke who were admitted to hospitals in Tyrol; 675 (14%) of the enrollees were treated with alteplase. Thrombolysis administration in Tyrol increased after programme implementation, from 160 of 1238 patients (12·9%, 95% CI 11·1-14·9) in 2010 to 213 of 1266 patients (16·8%, 14·8-19·0) in 2013 (ptrend 2010-13<0·0001). Differences in use of thrombolysis in the nine counties of Tyrol in 2010 (range, 2·2-22·6%) were reduced by 2013 (12·1-22·5%). Median statewide door-to-needle time decreased from 49 min (IQR 35-60) in 2010 to 44 min (29-60) in 2013; symptomatic post-thrombolysis intracerebral haemorrhages occurred in 28 of 675 patients (4·1%, 95% CI 2·8-5·9) during 2010-13. In four Austrian states without similar stroke programmes, thrombolysis administration remained stable or declined between 2010 and 2013 (mean reduction 14·4%, 95% CI 10·9-17·9). Although the 3-month mortality was not affected by our programme (137 [13%] of 1060 patients in 2010 vs 143 [13%] of 1069 patients in 2013), 3-month functional outcome significantly improved (modified Rankin Scale score 0-1 in 375 [40%] of 944 patients in 2010 vs 493 [53%] of 939 in 2013; score 0-2 in 531 [56%] patients in 2010 and 615 [65%] in 2013; ptrend 2010-13<0·0001). INTERPRETATION: During the period of implementation of our comprehensive stroke management programme, thrombolysis administration increased and clinical outcome significantly improved, although mortality did not change. We hope that these results will guide health authorities and stroke physicians elsewhere when implementing similar programmes for patients with stroke. FUNDING: Reformpool of the Tyrolean Health Care Fund.

Charge transport along proton wires.

Using density functional theory we look at the quantum mechanics of charge transport along water wires both with free ends and donor/acceptor terminated. With the intermediate geometries in the DFT iterations we can follow the charge transfer mechanism and also construct the energy landscape explicitly. It shows activation barriers when a proton is transferred from one water molecule to the next. This, together with snapshots of intermediate geometries, leads to a justification and further elucidation of the Grotthuss mechanism and the Bjerrum effect. The charge transfer times and the conductivity of the proton wire are obtained in agreement with experimental results.

Confinement and compression of an oligomer brush.

Self-assembled monolayers and oligomer brushes confined between two parallel plates show compressional forces that are nonmonotonic as a function of plate separation. In a realistic model of short alkanethiols, based on the rotationally isomeric state model with parameters from ab initio calculations, the authors show that nonmonotonic forces arise from the elimination of longer conformers as the distance between the plates is reduced. This nonmonotonicity is a size effect that disappears when the length of the polymer molecule is sufficiently increased. An analytical model is developed that allows experimentalists to extract energy-averaged brush height distributions from compressional force curves.

Stretching, unfolding, and deforming protein filaments adsorbed at solid-liquid interfaces using the tip of an atomic-force microscope.

Cells move by actively remodeling a dense network of protein filaments. Here we analyze the force response of various filaments in a simplified experimental setup, where single filaments are moved with an atomic-force microscope (AFM) tip against surface friction, with the AFM operating in the torsional mode. Our experimental findings are well explained within a simple model based on Newtonian mechanics: we observe force plateaus, which are the signature of the sequential stretching of single repeat units, followed ultimately by deformation of the whole polymer shape.

Model for stretching and unfolding the giant multidomain muscle protein using single-molecule force spectroscopy.

Single-molecule manipulation has allowed the forced unfolding of multidomain proteins. Here we outline a theory that not only explains these experiments but also points out a number of difficulties in their interpretation and makes suggestions for further experiments. For titin we reproduce force-extension curves, the dependence of break force on pulling speed, and break-force distributions and also validate two common experimental views: Unfolding titin Ig domains can be explained as stepwise increases in contour length, and increasing force peaks in native Ig sequences represent a hierarchy of bond strengths. Our theory is valid for essentially any molecule that can be unfolded in atomic force microscopy; as a further example, we present force-extension curves for the unfolding of RNA hairpins.

Breaking bonds in the atomic force microscope: extracting information.

A theoretical framework is developed to analyze molecular bond breaking in dynamic force spectroscopy using atomic force microscopy (AFM). An analytic expression of the observed bond breaking probability as a function of force is obtained in terms of the relevant physical parameters. Three different experimental realizations are discussed, in which (i) the force is increased linearly in time, and (ii) the AFM cantilever is moved at constant speed, and (iii) the force is held constant. We find that unique fitting of the bond parameters such as the potential depth and its width is possible only when data from rather different force-loading rates is used. The complications in the analysis of using the constant velocity mode arising from the intermediate polymer spacer are discussed at length.