Anomalous power law decay in solvation dynamics of DNA: a mode coupling theory analysis of ion contribution

Several time dependent fluorescence Stokes shift (TDFSS) experiments have reported a slow power law decay in the hydration dynamics of a DNA molecule. Such a power law has neither been observed in computer simulations nor in some other TDFSS experiments. Here we observe that a slow decay may originate from collective ion contribution because in experiments DNA is immersed in a buffer solution, and also from groove bound water and lastly from DNA dynamics itself. In this work we first express the solvation time correlation function in terms of dynamic structure factors of the solution. We use mode coupling theory to calculate analytically the time dependence of collective ionic contribution. A power law decay in seen to originate from an interplay between long-range probe–ion direct correlation function and ion–ion dynamic structure factor. Although the power law decay is reminiscent of Debye–Falkenhagen effect, yet solvation dynamics is dominated by ion atmosphere relaxation times at longer length scales (small wave number) than in electrolyte friction. We further discuss why this power law may not originate from water motions which have been computed by molecular dynamics simulations. Finally, we propose several experiments to check the prediction of the present theoretical work.     

Evaluation of blood plasma changes by differential scanning calorimetry in psoriatic patients treated with drugs

Psoriasis is a chronic inflammatory skin disease, most commonly resulting in the occurrence of red and silver scaly plaques. Application of differential scanning calorimetry (DSC) should be used as a new method to detect the different stages of the disease and to monitor medications with different anti-psoriatic drugs using patient’s blood plasma. The study included 72 white adults (35 men and 37 women; median age 56 years) with diagnosed psoriasis. According to the psoriasis area severity index (PASI) patients were selected into three groups: symptomless (PASI: 0), mild (PASI: 1–15), and serious symptoms (PASI: >15). According to medication patients were divided into untreated (n = 39) and treated (n = 33) groups. For systemic drug treatment cytostatic therapy (methotrexate, n = 12), retinoid treatment (acitretin, n = 10), and biologic response modifiers (adalimumab, n = 5; infliximab, n = 5; ustekinumab, n = 1) were applied. Denaturation of human plasma components were detected in Setaram Micro DSC II calorimeter. The patients had no third denaturation peak in the untreated mild and serious symptoms groups. In mild symptoms all the thermal parameters altered significantly, while in serious symptoms only the first melting and the calorimetric enthalpy altered significantly compared with symptoms-free states. In case of systematic cytostatic and retinoid drug treatment (methotrexate, n = 12; acitretin, n = 10) cases the DSC scans of patients with symptoms exhibited significant differences (p < 0.05) in melting temperatures and in calorimetric enthalpy compared with the untreated symptoms-free patients. Using biologic response modifier agents (adalimumab, infliximab, and ustekinumab) we had no enough samples for a statistical evaluation for each one, but after the intervention a stronger effect can be seen as in case of systematic drug treatment. In this study blood plasma measurement in psoriatic patients by DSC showed differences between untreated, conventional systemic drug treatment, and application of biologic response modifier agents, but further studies are needed to elucidate these relationships (supported by grant OTKA CO-272).     

Apparent wall slip velocity measurements in free surface flow of concentrated suspensions

In this work we have experimentally measured the apparent wall slip velocity in open channel flow of neutrally buoyant suspension of non-colloidal particles. The free surface velocity profile was measured using the tool of particle imaging velocimetry (PIV) for two different channels made of plane and rough walls. The rough walled channel prevents wall slip, whereas the plane wall showed significant wall slip due to formation of slip layer. By comparing the velocity profiles from these two cases we were able to determine the apparent wall slip velocity. This method allows characterization of wall slip in suspension of large sized particles which cannot be performed in conventional rheometers. Experiments were carried out for concentrated suspensions of various particle volume concentrations and for two different sizes of particles. It was observed that wall slip velocity increases with particle size and concentration but decreases with increase in the viscosity of suspending fluid. The apparent wall slip velocity coefficients are in qualitative agreement with the earlier measurements. The effect of wall slip on free surface corrugation was also studied by analyzing the power spectral density (PSD) of the refracted light from the free surface. Our results indicate that free surface corrugation is a bulk flow response and it does not arise from boundary problem such as development of slip layer.     

Ionic and dipolar solvation dynamics in liquid water

The solvation time correlation function for solvation in liquid water was measured recently. The solvation was found to be very fast, with a time constant equal to 55 fs. In this article we present theoretical studies on solvation dynamics of ionic and dipolar solutes in liquid water, based on the molecular hydrodynamic approach developed earlier. The molecular hydrodynamic theory can successfully predict the ultrafast dynamics of solvation in liquid water as observed from recent experiments. The present study also reveals some interesting aspects of dipolar solvation dynamics, which differs significantly from that of ionic solvation. Dedicated to Prof. C N R Rao on his 60th birthday     

A two-stage successive overrelaxation algorithm for solving the symmetric linear complementarity problem

We propose a two-stage successive overrelaxation method (TSOR) algorithm for solving the symmetric linear complementarity problem. After the first SOR preprocessing stage this algorithm concentrates on updating a certain prescribed subset of variables which is determined by exploiting the complementarity property. We demonstrate that this algorithm successfully solves problems with up to ten thousand variables.This material is based on research supported by National Science Foundation Grants DCR-8420963 and DCR-8521228 and Air Force Office of Scientific Research Grants AFSOR-86-0172 and AFSOR-86-0255 while the author was at the Computer Sciences Department at the University of Wisconsin-Madison, USA.     

Synthetic and characterization aspects of dimethylaminoethyl methacrylate reversible addition fragmentation chain transfer (RAFT) polymerization

2‐cyanoprop‐2‐yl dithiobenzoate (CPDB) mediated RAFT polymerization of dimethylaminoethyl methacrylate (DMAEMA) was carried out in dioxane at 90 °C. The influence of several parameters, such as the monomer to CPDB molar ratio (100 to 500), the monomer concentration (2 mol·L^?1 to 5.9 mol·L^?1), and CPDB to initiator molar ratio (1 to 10), was evaluated with regards to conversion and polymerization duration, as well as control of molar mass and molar mass distributions. Number average molar masses from 10,000 to 70,000 g·mol^?1 can be targeted. The determination of the molar masses has been carried out by size exclusion chromatography (SEC) with a refractometer detector with poly(methyl methacrylate) (PMMA) standards. The experimental values were lower than the expected ones. Then, SEC in aqueous medium with an online laser light scattering detector was used both to get absolute molar masses and to recalibrate the SEC column in THF. Characterization of well‐controlled PDMAEMA samples has been performed by proton NMR spectroscopy and matrix assisted laser desorption ionization time of flight mass spectrometry. Finally, a chain extension experiment was evaluated with regard to living features. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3551–3565, 2005     

On the molecular mechanism of drug intercalation into DNA: a simulation study of the intercalation pathway, free energy, and DNA structural changes

Intercalation into DNA (insertion between a pair of base pairs) is a critical step in the function of many anticancer drugs. Despite its importance, a detailed mechanistic understanding of this process at the molecular level is lacking. We have constructed, using extensive atomistic computer simulations and umbrella sampling techniques, a free energy landscape for the intercalation of the anticancer drug daunomycin into a twelve base pair B-DNA. A similar free energy landscape has been constructed for a probable intermediate DNA minor groove-bound state. These allow a molecular level understanding of aspects of the thermodynamics, DNA structural changes, and kinetic pathways of the intercalation process. Key DNA structural changes involve opening the future intercalation site base pairs toward the minor groove (positive roll), followed by an increase in the rise, accompanied by hydrogen bonding changes of the minor groove waters. The calculated intercalation free energy change is -12.3 kcal/mol, in reasonable agreement with the experimental estimate -9.4 kcal/mol. The results point to a mechanism in which the drug first binds to the minor groove and then intercalates into the DNA in an activated process, which is found to be in general agreement with experimental kinetic results.     

Non-monotonic, distance-dependent relaxation of water in reverse micelles: propagation of surface induced frustration along hydrogen bond networks

Layer-wise, distance-dependent orientational relaxation of water confined in reverse micelles (RM) is studied using theoretical and computational tools. We use both a newly constructed "spins on a ring" (SOR) Ising-type model (with Shore-Zwanzig rotational dynamics) and atomistic simulations with explicit water. Our study explores the effect of reverse micelle size and role of intermolecular correlations, compromised by the presence of a highly polar surface, on the distance (from the interface) dependence of water relaxation. The "spins on a ring" model can capture some aspects of distance dependence of relaxation, such as acceleration of orientational relaxation at intermediate layers. In atomistic simulations, layer-wise decomposition of hydrogen bond formation pattern clearly reveals that hydrogen bond arrangement of water at a certain distance away from the surface can remain frustrated due to the interaction with the polar surface head groups. This layer-wise analysis also reveals the presence of a non-monotonic slow relaxation component which can be attributed to this frustration effect and which is accentuated in small to intermediate size RMs. For large size RMs, the long time component decreases monotonically from the interface to the interior of the RMs with slowest relaxation observed at the interface.     

Patterned Silk Film Scaffolds for Aligned Lamellar Bone Tissue Engineering

The alignment and osteogenic differentiation of MSCs on patterned silk films (PF) is investigated as a bottom‐up approach toward engineering bone lamellae. Screening PF with various groove dimensions shows that cell alignment is mediated by both the pattern width and depth. MSCs are differentiated in osteogenic medium for four weeks on flat films and on the PF that produce the best alignment. The PF support osteogenic differentiation while also inducing lamellar alignment of cells and matrix deposition. A secondary alignment effect is noted on the PF where a new layer of aligned cells grows over the first layer, but rotated obliquely to the underlying pattern. This layering and rotation of the MSCs resembles the cellular organization observed in native lamellar bone.