DNA-Protein Binding Rates: Bending Fluctuation and Hydrodynamic Coupling Effects

We investigate diffusion-limited reactions between a diffusing particle and a target site on a semiflexible polymer, a key factor determining the kinetics of DNA-protein binding and polymerization of cytoskeletal filaments. Our theory focuses on two competing effects: polymer shape fluctuations, which speed up association, and the hydrodynamic coupling between the diffusing particle and the chain, which slows down association. Polymer bending fluctuations are described using a mean field dynamical theory, while the hydrodynamic coupling between polymer and particle is incorporated through a simple heuristic approximation. Both of these we validate through comparison with Brownian dynamics simulations. Neither of the effects has been fully considered before in the biophysical context, and we show they are necessary to form accurate estimates of reaction processes. The association rate depends on the stiffness of the polymer and the particle size, exhibiting a maximum for intermediate persistence length and a minimum for intermediate particle radius. In the parameter range relevant to DNA-protein binding, the rate increase is up to 100% compared to the Smoluchowski result for simple center-of-mass motion. The quantitative predictions made by the theory can be tested experimentally.Comment: 21 pages, 11 figures, 1 tabl

Substrate concentration dependence of the diffusion-controlled steady-state rate constant

The Smoluchowski approach to diffusion-controlled reactions is generalized to interacting substrate particles by including the osmotic pressure and hydrodynamic interactions of the nonideal particles in the Smoluchoswki equation within a local-density approximation. By solving the strictly linearized equation for the time-independent case with absorbing boundary conditions, we present an analytic expression for the diffusion-limited steady-state rate constant for small substrate concentrations in terms of an effective second virial coefficient B_2*. Comparisons to Brownian dynamics simulations excluding HI show excellent agreement up to bulk number densities of B_2* rho_0 < 0.4 for hard sphere and repulsive Yukawa-like interactions between the substrates. Our study provides an alternative way to determine the second virial coefficient of interacting macromolecules experimentally by measuring their steady-state rate constant in diffusion-controlled reactions at low densities.Comment: 7 pages, 3 figure

Shear-induced reaction-limited aggregation kinetics of Brownian particles at arbitrary concentrations

The aggregation of interacting Brownian particles in sheared concentrated suspensions is an important issue in colloid and soft matter science per se. Also, it serves as a model to understand biochemical reactions occurring in vivo where both crowding and shear play an important role. We present an effective medium approach within the Smoluchowski equation with shear which allows one to calculate the encounter kinetics through a potential barrier under shear at arbitrary colloid concentrations. Experiments on a model colloidal system in simple shear flow support the validity of the model in the range considered. By generalizing Kramers' rate theory to the presence of collective hydrodynamics, our model explains the significant increase in the shear-induced reaction-limited aggregation kinetics upon increasing the colloid concentration

To swim or not to swim: an interpretation of farmed mink's motivation for a water bath

How an animal’s behavioural (ethological) needs can be met is a pivotal issue in the assessment of welfare for captive animals. The value of swimming water for farmed mink is an example how scientific and societal questions relating to animal welfare can be answered. A number of studies have addressed the issue of the indispensability of swimming water for mink; however, so far with inconclusive evidence. In this paper, the results of these studies and related literature are reviewed. First, the biological definition of need is discussed. Subsequently, attention is paid to the effects of the presence, absence and the removal of swimming water on behavioural and physiological correlates of well-being including stereotypic and anticipatory behaviour and urinary cortisol. Thereafter we discuss individual differences in the use of swimming water, the price animals pay for access to a water bath, and the effect of access to swimming water on juvenile play. The main conclusions of the literature review are that 1) the use of a water bath for mink is most likely related to foraging behaviour (foraging areas: land and water); 2) absence of swimming water, without prior experience, does not lead to consistent changes in level of stereotypic behaviour, or anticipatory responses; 3) removal of a previously experienced water bath may induce short-term stress as indicated by behavioural parameters and elevated cortisol responses; 4) mink work hard for access to a swimming bath and running wheel in consumer demand studies. Other cage modifications such as tunnels and biting objects, may also provide environmental enrichment, if they are added to otherwise impoverished conditions; 5) There are individual differences in the use of swimming water: these are related in part to variation in prior experience of aquatic resources.; 6) As prior experience is important both with respect to individual use of swimming water and the response to deprivation, swimming water can not be described as biological need in the sense of a fixed requirement for survival. As swimming water appears to act as an incentive that induces its own motivation a more accurate term may be an “incentive induced or environmentally facilitated need”. Given the available evidence, it is not possible to conclude whether mink that have never experienced swimming water, suffer as a consequence of its absence. However, it is possible to predict that mink with access to water have improved quality of life, due to increased behavioural opportunities, in comparison to farmed mink without access to swimming water. In practical terms, it is still open to debate whether mink should be provided with swimming water, or if alternative, less valued, but easier to install and maintain forms of environmental enrichment, should be provided in mink housing. To clarify these issues a number of future studies would be valuable. These include; 1) whether specific environmental cues affect motivation to swim, such as the form of drinking water delivery systems ; 2) whether prior experience of swimming water affects its incentive value; in other words “can you miss what you never experienced?”; 3) do behavioural parameters such as stereotypic behaviour; rebound effects and vacuum activity have any general utility in assessing the value of absent resources; 4) what are preferences for and the value of alternative resources which may act as substitutes for swimming water. In addition we would recommend further work investigating: relationship between access to swimming water and positive indicators of welfare such as play and/or anticipatory behaviour; the effects of preventing the performance of rewarding behaviours and deprivation of a previous experienced resource; and health and hygeine issues related to provision of a water bath. In future work, it would be desirable to present be the actual percentages of animals using a water bath during the experiment and the use of power analyses, to aid their interpretation

A large stellar evolution database for population synthesis studies: VI. White dwarf cooling sequences

We present a new set of cooling models and isochrones for both H- and He-atmosphere white dwarfs, incorporating accurate boundary conditions from detailed model atmosphere calculations, and carbon-oxygen chemical abundance profiles based on updated stellar evolution calculations from the BaSTI stellar evolution archive - a theoretical data center for the Virtual Observatory. We discuss and quantify the uncertainties in the cooling times predicted by the models, arising from the treatment of mixing during the central H- and He-burning phases, number of thermal pulses experienced by the progenitors, progenitor metallicity and the $^{12}C(\alpha,\gamma)^{16}O$ reaction rate. The largest sources of uncertainty turn out to be related to the treatment of convection during the last stages of the progenitor central He-burning phase, and the $^{12}C(\alpha,\gamma)^{16}O$ reaction rate. We compare our new models to previous calculations performed with the same stellar evolution code, and discuss their application to the estimate of the age of the solar neighborhood, and the interpretation of the observed number ratios between H- and He-atmosphere white dwarfs. The new white dwarf sequences and an extensive set of white dwarf isochrones that cover a large range of ages and progenitor metallicities are made publicly available at the official BaSTI website.Comment: 34 pages, 13 figures, The Astrophysical Journal, in pres

The white dwarf cooling sequence in the old open cluster NGC 188

We develop the white dwarf luminosity function (LF) of the old open cluster NGC 188 in order to determine a lower limit to the age of the cluster by using the faint end of the cooling sequence. To produce an extensive sequence of the cooling white dwarfs we imaged four contiguous HST-WFPC2 fields in the center of the cluster in the F555W and F814W filters. After imposing selection criteria on the detected objects we found a white dwarf cooling sequence (down to V ~26.5) including 28 candidate white dwarfs in the cluster. The exposures are not deep enough to reach the end of this sequence, but the results of our analysis allow us to establish a lower limit to the age of the cluster independently of the isochrone fit to the cluster turnoff. The most ancient white dwarfs found are ~4 Gyr old, an age that is set solely by the photometric limit of our data. Classical methods provide an estimate of \~7 Gyr (Sarajedini et al., 1999).Comment: 6 pages, 5 figures, accepted on Astronomy and Astrophysic

Kramers rate theory of ionization and dissociation of bound states

Calculating the microscopic dissociation rate of a bound state, such as a classical diatomic molecule, has been difficult so far. The problem was that standard theories require an energy barrier over which the bound particle (or state) escapes into the preferred low-energy state. This is not the case when the long-range repulsion responsible for the barrier is either absent or screened (as in Cooper pairs, ionized plasma, or biomolecular complexes). We solve this classical problem by accounting for entropic memory at the microscopic level. The theory predicts dissociation rates for arbitrary potentials and is successfully tested on the example of plasma, where it yields an estimate of ionization in the core of Sun in excellent agreement with experiments. In biology, the new theory accounts for crowding in receptor-ligand kinetics and protein aggregation

Prediction of the Atomization Energy of Molecules Using Coulomb Matrix and Atomic Composition in a Bayesian Regularized Neural Networks

Exact calculation of electronic properties of molecules is a fundamental step for intelligent and rational compounds and materials design. The intrinsically graph-like and non-vectorial nature of molecular data generates a unique and challenging machine learning problem. In this paper we embrace a learning from scratch approach where the quantum mechanical electronic properties of molecules are predicted directly from the raw molecular geometry, similar to some recent works. But, unlike these previous endeavors, our study suggests a benefit from combining molecular geometry embedded in the Coulomb matrix with the atomic composition of molecules. Using the new combined features in a Bayesian regularized neural networks, our results improve well-known results from the literature on the QM7 dataset from a mean absolute error of 3.51 kcal/mol down to 3.0 kcal/mol.Comment: Under review ICANN 201

Outer boundary conditions for evolving cool white dwarfs

White dwarf evolution is essentially a gravothermal cooling process, which,for cool white dwarfs, sensitively depends on the treatment of the outer boundary conditions. We provide detailed outer boundary conditions appropriate for computing the evolution of cool white dwarfs employing detailed non-gray model atmospheres for pure H composition. We also explore the impact on the white dwarf cooling times of different assumptions for energy transfer in the atmosphere of cool white dwarfs. Detailed non-gray model atmospheres are computed taken into account non-ideal effects in the gas equation of state and chemical equilibrium, collision-induced absorption from molecules, and the Lyman alpha quasi-molecular opacity. Our results show that the use of detailed outer boundary conditions becomes relevant for effective temperatures lower than 5800 and 6100K for sequences with 0.60 and 0.90 M_sun, respectively. Detailed model atmospheres predict ages that are up to approx 10% shorter at log L/L_sun=-4 when compared with the ages derived using Eddington-like approximations at tau_Ross=2/3. We also analyze the effects of various assumptions and physical processes of relevance in the calculation of outer boundary conditions. In particular, we find that the Ly_alpha red wing absorption does not affect substantially the evolution of white dwarfs. White dwarf cooling timescales are sensitive to the surface boundary conditions for T_eff < 6000K. Interestingly enough, non-gray effects have little consequences on these cooling times at observable luminosities. In fact, collision-induced absorption processes, which significantly affect the spectra and colors of old white dwarfs with hydrogen-rich atmospheres, have not noticeable effects in their cooling rates, except throughout the Rosseland mean opacity.Comment: 6 pages, 9 figures, to be published in Astronomy and Astrophysic

The Spectral Energy Distributions of White Dwarfs in 47 Tucanae: The Distance to the Cluster

We present a new distance determination to the Galactic globular cluster 47 Tucanae by fitting the spectral energy distributions of its white dwarfs to pure hydrogen atmosphere white dwarf models. Our photometric dataset is obtained from a 121 orbit Hubble Space Telescope program using the Wide Field Camera 3 UVIS/IR channels, capturing F390W, F606W, F110W, and F160W images. These images cover more than 60 square arcmins and extend over a radial range of 5-13.7 arcmin (6.5-17.9 pc) within the globular cluster. Using a likelihood analysis, we obtain a best fitting unreddened distance modulus of (m - M)o=13.36+/-0.02+/-0.06 corresponding to a distance of 4.70+/-0.04+/-0.13 kpc, where the first error is random and the second is systematic. We also search the white dwarf photometry for infrared excess in the F160W filter, indicative of debris disks or low mass companions, and find no convincing cases within our sample.Comment: Accepted to The Astronomical Journal, 13 Figures, 2 Tables. Figures 3 and 6 are figure sets, each composed of 59 subfigures (to appear in the electronic journal). This is a Companion paper to the article ID: submit/037561