Dielectric constant and ionic strength effects on DNA precipitation

We have investigated the effect of different zwitterionic compounds on DNA precipitation induced by spermine4+. Glycine, beta-alanine, 4-aminobutyric acid, and 6-aminocaproic acid have shown an increasing capacity to attenuate DNA precipitation. This protection effect has been correlated with the dielectric constant increase of their corresponding solutions. Calculations based on these experimental data and counter-ion condensation theory have confirmed the importance of this parameter for DNA-ion interactions and precipitation mechanisms. We have also observed a resolubilization of DNA in the presence of 6-aminocaproic acid at high spermine4+ concentration and in the presence of glycine at high spermidine3+ concentration. This could be explained by an increase of screening effect with polyamine concentration

Simulation of Preterm Neonatal Brain Metabolism During Functional Neuronal Activation Using a Computational Model

We present a computational model of metabolism in the preterm neonatal brain. The model has the capacity to mimic haemodynamic and metabolic changes during functional activation and simulate functional near-infrared spectroscopy (fNIRS) data. As an initial test of the model's efficacy, we simulate data obtained from published studies investigating functional activity in preterm neonates. In addition we simulated recently collected data from preterm neonates during visual activation. The model is well able to predict the haemodynamic and metabolic changes from these observations. In particular, we found that changes in cerebral blood flow and blood pressure may account for the observed variability of the magnitude and sign of stimulus-evoked haemodynamic changes reported in preterm infants

Patterns in random walks and Brownian motion

We ask if it is possible to find some particular continuous paths of unit length in linear Brownian motion. Beginning with a discrete version of the problem, we derive the asymptotics of the expected waiting time for several interesting patterns. These suggest corresponding results on the existence/non-existence of continuous paths embedded in Brownian motion. With further effort we are able to prove some of these existence and non-existence results by various stochastic analysis arguments. A list of open problems is presented.Comment: 31 pages, 4 figures. This paper is published at http://link.springer.com/chapter/10.1007/978-3-319-18585-9_

Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives

To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue

Estimating patient specific uncertainty parameters for adaptive treatment re-planning in proton therapy using in vivo range measurements and Bayesian inference: Application to setup and stopping power errors

In proton therapy, quanti cation of the proton range uncertainty is important to achieve dose distribution compliance. The promising accuracy of prompt gamma imaging (PGI) suggests the development of a mathematical framework using the range measurements to convert population based estimates of uncertainties into patient speci c estimates with the purpose of plan adaptation. We present here such framework using Bayesian inference. The sources of uncertainty were modeled by three parameters: setup bias m, random setup precision r and water equivalent path length bias u. The evolution of the expectation values E(m), E(r) and E(u) during the treatment was simulated. The expectation values converged towards the true simulation parameters after 5 and 10 fractions, for E(m) and E(u), respectively. E(r) settle on a constant value slightly lower than the true value after 10 fractions. In conclusion, the simulation showed that there is enough information in the frequency distribution of the range errors measured by PGI to estimate the expectation values and the con dence interval of the model parameters by Bayesian inference. The updated model parameters were used to compute patient speci c lateral and local distal margins for adaptive re-planning

23Na NMR study of the effect of organic osmolytes on DNA counterion atmosphere.

The effect of different organic osmolytes on the DNA counterion condensation layer has been investigated by 23Na NMR relaxation measurements. The zwitterionic compounds glycine, beta-alanine, 4-aminobutyric acid, and 6-aminocaproic acid have shown an increasing capacity to decrease the amount of sodium ions in the vicinity of the macromolecule. The experimental data have been correlated with the dielectric constant increase in their corresponding solutions and have been compared with the prediction of counterion condensation theory. Polyols (sorbitol and mannitol) did not display the same effect. These compounds largely increase the relaxation rate of sodium ions in the proximity of DNA, unlike the zwitterionic compounds. This probably results from a perturbation of the water dynamic around the macromolecule, of the primary or secondary hydration shell of the sodium nuclei involved, or both