A model for melting of confined DNA

When DNA molecules are heated they denature. This occurs locally so that loops of molten single DNA strands form, connected by intact double-stranded DNA pieces. The properties of this "melting" transition have been intensively investigated. Recently there has been a surge of interest in this question, caused by experiments determining the properties of partially bound DNA confined to nanochannels. But how does such confinement affect the melting transition? To answer this question we introduce, and solve a model predicting how confinement affects the melting transition for a simple model system by first disregarding the effect of self-avoidance. We find that the transition is smoother for narrower channels. By means of Monte-Carlo simulations we then show that a model incorporating self-avoidance shows qualitatively the same behaviour and that the effect of confinement is stronger than in the ideal case.Comment: 5 pages, 4 figures, supplementary materia

Probing the Solar Atmosphere Using Oscillations of Infrared CO Spectral Lines

Oscillations were observed across the whole solar disk using the Doppler shift and line depth of spectral lines from the CO molecule near 4666~nm with the National Solar Observatory's McMath/Pierce solar telescope. Power, coherence, and phase spectra were examined, and diagnostic diagrams reveal power ridges at the solar global mode frequencies to show that these oscillations are solar p-modes. The phase was used to determine the height of formation of the CO lines by comparison with the IR continuum intensity phase shifts as measured in Kopp et al., 1992; we find the CO line formation height varies from 425 < z < 560 km as we move from disk center towards the solar limb 1.0 > mu > 0.5. The velocity power spectra show that while the sum of the background and p-mode power increases with height in the solar atmosphere as seen in previous work, the power in the p-modes only (background subtracted) decreases with height, consistent with evanescent waves. The CO line depth weakens in regions of stronger magnetic fields, as does the p-mode oscillation power. Across most of the solar surface the phase shift is larger than the expected value of 90 degrees for an adiabatic atmosphere. We fit the phase spectra at different disk positions with a simple atmospheric model to determine that the acoustic cutoff frequency is about 4.5 mHz with only small variations, but that the thermal relaxation frequency drops significantly from 2.7 to 0 mHz at these heights in the solar atmosphere

The cellular heat shock response monitored by chemical exchange saturation transfer MRI

CEST-MRI of the rNOE signal has been demonstrated in vitro to be closely linked to the protein conformational state. As the detectability of denaturation and aggregation processes on a physiologically relevant scale in living organisms has yet to be verified, the aim of this study was to perform heat-shock experiments with living cells to monitor the cellular heat-shock response of the rNOE CEST signal. Cancer cells (HepG2) were dynamically investigated after a mild, non-lethal heat-shock of 42 °C for 20 min using an MR-compatible bioreactor system at 9.4 T. Reliable and fast high-resolution CEST imaging was realized by a relaxation-compensated 2-point contrast metric. After the heat-shock, a substantial decrease of the rNOE CEST signal by 8.0 ± 0.4% followed by a steady signal recovery within a time of 99.1 ± 1.3 min was observed in two independent trials. This continuous signal recovery is in coherence with chaperone-induced refolding of heat-shock induced protein aggregates. We demonstrated that protein denaturation processes influence the CEST-MRI signal on a physiologically relevant scale. Thus, the protein folding state is, along with concentration changes, a relevant physiological parameter for the interpretation of CEST signal changes in diseases that are associated with pathological changes in protein expression, like cancer and neurodegenerative diseases

Nanoconfined circular and linear DNA - equilibrium conformations and unfolding kinetics

Studies of circular DNA confined to nanofluidic channels are relevant both from a fundamental polymer-physics perspective and due to the importance of circular DNA molecules in vivo. We here observe the unfolding of DNA from the circular to linear configuration as a light-induced double strand break occurs, characterize the dynamics, and compare the equilibrium conformational statistics of linear and circular configurations. This is important because it allows us to determine to which extent existing statistical theories describe the extension of confined circular DNA. We find that the ratio of the extensions of confined linear and circular DNA configurations increases as the buffer concentration decreases. The experimental results fall between theoretical predictions for the extended de Gennes regime at weaker confinement and the Odijk regime at stronger confinement. We show that it is possible to directly distinguish between circular and linear DNA molecules by measuring the emission intensity from the DNA. Finally, we determine the rate of unfolding and show that this rate is larger for more confined DNA, possibly reflecting the corresponding larger difference in entropy between the circular and linear configurations.Comment: 21 pages, 7 figures, 1 tabl

impulsivity and the impact of contextual cues on instrumental behavior in alcohol dependence

Alcohol-related cues acquire incentive salience through Pavlovian conditioning and then can markedly affect instrumental behavior of alcohol-dependent patients to promote relapse. However, it is unclear whether similar effects occur with alcohol-unrelated cues. We tested 116 early-abstinent alcohol- dependent patients and 91 healthy controls who completed a delay discounting task to assess choice impulsivity, and a Pavlovian-to-instrumental transfer (PIT) paradigm employing both alcohol-unrelated and alcohol-related stimuli. To modify instrumental choice behavior, we tiled the background of the computer screen either with conditioned stimuli (CS) previously generated by pairing abstract pictures with pictures indicating monetary gains or losses, or with pictures displaying alcohol or water beverages. CS paired to money gains and losses affected instrumental choices differently. This PIT effect was significantly more pronounced in patients compared to controls, and the group difference was mainly driven by highly impulsive patients. The PIT effect was particularly strong in trials in which the instrumental stimulus required inhibition of instrumental response behavior and the background CS was associated to monetary gains. Under that condition, patients performed inappropriate approach behavior, contrary to their previously formed behavioral intention. Surprisingly, the effect of alcohol and water pictures as background stimuli resembled that of aversive and appetitive CS, respectively. These findings suggest that positively valenced background CS can provoke dysfunctional instrumental approach behavior in impulsive alcohol- dependent patients. Consequently, in real life they might be easily seduced by environmental cues to engage in actions thwarting their long-term goals. Such behaviors may include, but are not limited to, approaching alcohol

Superconductivity in Undoped BaFe2As2 by Tetrahedral Geometry Design

Fe-based superconductors exhibit a diverse interplay between charge, orbital, and magnetic ordering1-4. Variations in atomic geometry affect electron hopping between Fe atoms5,6 and the Fermi surface topology, influencing magnetic frustration and the pairing mechanism through changes of orbital overlap and occupancies7-11. Here, we experimentally demonstrate a systematic approach to realize superconductivity without chemical doping in BaFe2As2, employing geometric design within an epitaxial heterostructure. We control both tetragonality and orthorhombicity in BaFe2As2 through superlattice engineering, which we experimentally find to induce superconductivity when the As-Fe-As bond angle approaches that in a regular tetrahedron. This approach of superlattice design could lead to insights into low dimensional superconductivity in Fe-based superconductors

Recent Developments in Helioseismic Analysis Methods and Solar Data Assimilation

MR and AS have received funding from the European Research Council under the European Union’s Seventh Framework Program (FP/2007-2013)/ERC Grant Agreement no. 307117