Statistical properties of metastable intermediates in DNA unzipping

We unzip DNA molecules using optical tweezers and determine the sizes of the cooperatively unzipping and zipping regions separating consecutive metastable intermediates along the unzipping pathway. Sizes are found to be distributed following a power law, ranging from one base pair up to more than a hundred base pairs. We find that a large fraction of unzipping regions smaller than 10 bp are seldom detected because of the high compliance of the released single stranded DNA. We show how the compliance of a single nucleotide sets a limit value around 0.1 N/m for the stiffness of any local force probe aiming to discriminate one base pair at a time in DNA unzipping experiments.Comment: Main text: 4 pages, 3 figures. Supplementary Information: 18 pages, 15 figure

Conformally related massless fields in dS, AdS and Minkowski spaces

In this paper we write down the equation for a scalar conformally coupled field simultaneously for de Sitter (dS), anti-de Sitter (AdS) and Minkowski spacetime in d-dimensions. The curvature dependence appears in a very simple way through a conformal factor. As a consequence the process of curvature free limit, including wave functions limit and two-points functions, turns to be a straightforward issue. We determine a set of modes, that we call de Sitter plane waves, which become ordinary plane waves when the curvature vanishes.Comment: 7 pages, 1 figur

Developing a Macroscopic Mechanistic Model for Low Molecular Weight Diffusion through Polymers in the Rubbery State

Raman microspectroscopy was used to determine the Fickian diffusivity of two families of low molecular weight molecules through amorphous polystyrene in the rubbery state. Different effects of the temperature on diffusivity for each of the families suggested that molecular mobility is controlled by both the volume and flexibility of the diffusing substance when the movement of polymer chains can generate stress induced deformation of molecules. The diffusing molecules were represented as Newtonian spring-bead systems, which allowed us to quantify their flexibility, in function of the vibration frequency of their bonds by reconstructing their theoretical spectra. Results showed that the use of molecular descriptors that take into account flexibility rather than the most stable conformation of the diffusing molecules may improve the description of the diffusion behavior caused by variations in shape and size of the free volumes of the polymeric matrix in the rubbery state

Dynamic force spectroscopy of DNA hairpins. II. Irreversibility and dissipation

We investigate irreversibility and dissipation in single molecules that cooperatively fold/unfold in a two state manner under the action of mechanical force. We apply path thermodynamics to derive analytical expressions for the average dissipated work and the average hopping number in two state systems. It is shown how these quantities only depend on two parameters that characterize the folding/unfolding kinetics of the molecule: the fragility and the coexistence hopping rate. The latter has to be rescaled to take into account the appropriate experimental setup. Finally we carry out pulling experiments with optical tweezers in a specifically designed DNA hairpin that shows two-state cooperative folding. We then use these experimental results to validate our theoretical predictions.Comment: 28 pages, 12 figure

Improving signal-to-noise resolution in single molecule experiments using molecular constructs with short handles

We investigate unfolding/folding force kinetics in DNA hairpins exhibiting two and three states with newly designed short dsDNA handles (29 bp) using optical tweezers. We show how the higher stiffness of the molecular setup moderately enhances the signal-to-noise ratio (SNR) in hopping experiments as compared to conventional long handles constructs (approximately 700 bp). The shorter construct results in a signal of higher SNR and slower folding/unfolding kinetics, thereby facilitating the detection of otherwise fast structural transitions. A novel analysis of the elastic properties of the molecular setup, based on high-bandwidth measurements of force fluctuations along the folded branch, reveals that the highest SNR that can be achieved with short handles is potentially limited by the marked reduction of the effective persistence length and stretch modulus of the short linker complex.Comment: Main paper: 20 pages and 6 figures. Supplementary Material: 25 page

There are no multiply-perfect Fibonacci numbers

Here, we show that no Fibonacci number (larger than 1) divides the sum of its divisors

Cutaneous metastases from cholangiocarcinoma following percutaneous transhepatic biliary drainage: Case report and literature review

AbstractPercutaneous transhepatic biliary drainage (PTBD) is commonly used in the management of cholangiocarcioma. Major and minor complications of PTBD such as cholangitis, haemorrhage and catheter dislocation are well documented. A lesser reported complication are cutaneous metastases following PTBD for cholangiocarcinoma.We report a case of a 79 year old man who presented with right upper quadrant pain, jaundice and weight loss, with dilated intra-hepatic bile ducts on imaging. The cytology results from a sample taken during endoscopic retrograde cholangiopancreatography were highly suspicious of cholangiocarcioma. A PTBD was subsequently performed and bilateral metal biliary stents were placed without external drainage. Five months after the PTBD he was found to have a hard nodule under the PTBD puncture site. The nodule was excised and the histology confirmed a cholangiocarcinoma metastasis.A review of the literature identified twelve cases of cutaneous metastases from cholangiocarcinoma, following PTBD. In addition, tumour seeding along the catheter tract following PTBD, with metastatic deposits on the abdominal wall, peritoneoum, chest wall, pleural space, and liver parenchyma have also been reported.Health care professionals should be aware of this rare complication and offer appropriate management options to patients

Dynamic force spectroscopy of DNA hairpins. I. Force kinetics and free energy landscapes

We investigate the thermodynamics and kinetics of DNA hairpins that fold/unfold under the action of applied mechanical force. We introduce the concept of the molecular free energy landscape and derive simplified expressions for the force dependent Kramers-Bell rates. To test the theory we have designed a specific DNA hairpin sequence that shows two-state cooperative folding under mechanical tension and carried out pulling experiments using optical tweezers. We show how we can determine the parameters that characterize the molecular free energy landscape of such sequence from rupture force kinetic studies. Finally we combine such kinetic studies with experimental investigations of the Crooks fluctuation relation to derive the free energy of formation of the hairpin at zero force.Comment: 28 pages, 12 figure

De Sitter Waves and the Zero Curvature Limit

We show that a particular set of global modes for the massive de Sitter scalar field (the de Sitter waves) allows to manage the group representations and the Fourier transform in the flat (Minkowskian) limit. This is in opposition to the usual acceptance based on a previous result, suggesting the appearance of negative energy in the limit process. This method also confirms that the Euclidean vacuum, in de Sitter spacetime, has to be preferred as far as one wishes to recover ordinary QFT in the flat limit.Comment: 9 pages, latex no figure, to appear in Phys. Rev.