Simulated acoustic emissions from coupled strings

We consider traveling transverse waves on two identical uniform taut strings that are elastically coupled through springs that gradually decrease their stiffness over a region of finite length. The wave system can be decomposed into two modes: an in-phase mode ( + ) that is transparent to the coupling springs, and an out-of-phase mode ( − ) that engages the coupling springs and can resonate at a particular location depending on the excitation frequency. The system exhibits linear mode conversion whereby an incoming ( + ) wave is reflected back from the resonance location both as a propagating ( + ) wave and an evanescent ( − ) wave, while both types emerge as propagating forward through the resonance location. We match a local transition layer expansion to the WKB expansion to obtain estimates of the reflection and transmission coefficients. The reflected waves may be an analog for stimulated emissions from the ear

Abrupt Transition from a Free, Repulsive to a Condensed, Attractive DNA Phase, Induced by Multivalent Polyamine Cations

We have investigated the energetics of DNA condensation by multivalent polyamine cations. Solution small angle x-ray scattering was used to monitor interactions between short 25 base pair dsDNA strands in the free supernatant DNA phase that coexists with the condensed DNA phase. Interestingly, when tetravalent spermine is used, significant inter-DNA repulsion is observed in the free phase, in contrast with the presumed inter-DNA attraction in the coexisting condensed phase. DNA condensation thus appears to be a discrete, first-order-like, transition from a repulsive gaseous to an attractive condensed solid phase, in accord with the reported all-or-none condensation of giant DNA. We further quantify the electrostatic repulsive potentials in the free DNA phase and estimate the number of additional spermine cations that bind to DNA upon condensation

Measuring Inter-DNA Potentials in Solution

Interactions between short strands of DNA can be tuned from repulsive to attractive by varying solution conditions and have been quantified using small angle x-ray scattering techniques. The effective DNA interaction charge was extracted by fitting the scattering profiles with the generalized one-component method and inter-DNA Yukawa pair potentials. A significant charge is measured at low to moderate monovalent counterion concentrations, resulting in strong inter-DNA repulsion. The charge and repulsion diminish rapidly upon the addition of divalent counterions. An intriguing short range attraction is observed at surprisingly low divalent cation concentrations, ~16 mM Mg2+. Quantitative measurements of inter- DNA potentials are essential for improving models of fundamental interactions in biological systems

Inter-DNA Attraction Mediated by Divalent Counterions

Can nonspecifically bound divalent counterions induce attraction between DNA strands? Here, we present experimental evidence demonstrating attraction between short DNA strands mediated by Mg2 ions. Solution small angle x-ray scattering data collected as a function of DNA concentration enable model independent extraction of the second virial coefficient. As the [Mg2] increases, this coefficient turns from positive to negative reflecting the transition from repulsive to attractive inter-DNA interaction. This surprising observation is corroborated by independent light scattering experiments. The dependence of the observed attraction on experimental parameters including DNA length provides valuable clues to its origin

Mono- and Trivalent Ions around DNA: A Small-Angle Scattering Study of Competition and Interactions

The presence of small numbers of multivalent ions in DNA-containing solutions results in strong attractive forces between DNA strands. Despite the biological importance of this interaction, e.g., DNA condensation, its physical origin remains elusive.Wecarried out a series of experiments to probe interactions between short DNA strands as small numbers of trivalent ions are included in a solution containing DNA and monovalent ions. Using resonant (anomalous) and nonresonant small angle x-ray scattering, we coordinated measurements of the number and distribution of each ion species around the DNA with the onset of attractive forces between DNA strands. DNA-DNA interactions occur as the number of trivalent ions increases. Surprisingly good agreement is found between data and size-corrected numerical Poisson-Boltzmann predictions of ion competition for non- and weakly interacting DNAs. We also obtained an estimate for the minimum number of trivalent ions needed to initiate DNA-DNA attraction

Focusing Capillary Optics for Use in Solution Small-Angle X-Ray Scattering

Measurements of the global conformation of macromolecules can be carried out using small-angle X-ray scattering (SAXS). Glass focusing capillaries, manufactured at the Cornell High Energy Synchrotron Source (CHESS), have been successfully employed for SAXS measurements on the heme protein cytochrome c. These capillaries provide high X-ray flux into a spot size of tens of micrometres, permitting short exposures of small-volume samples. Such a capability is ideal for use in conjunction with microfluidic mixers, where time resolution may be determined by beam size and sample volumes are kept small to facilitate mixing and conserve material

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development

Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema

Spatial Distribution of Competing Ions around DNA in Solution

The competition of monovalent and divalent cations for proximity to negatively charged DNA is of biological importance and can provide strong constraints for theoretical treatments of polyelectrolytes. Resonant x-ray scattering experiments have allowed us to monitor the number and distribution of each cation in a mixed ion cloud around DNA. These measurements provide experimental evidence to support a general theoretical prediction: the normalized distribution of each ion around polyelectrolytes remains constant when ions are mixed at different ratios. In addition, the amplitudes of the scattering signals throughout the competition provide a measurement of the surface concentration parameter that predicts the competition behavior of these cations. The data suggest that ion size needs to be taken into account in applying Poisson-Boltzmann treatments to polyelectrolytes such as DNA

Prehospital randomised assessment of a mechanical compression device in cardiac arrest (PaRAMeDIC) trial protocol

Background Survival after out-of-hospital cardiac arrest is closely linked to the quality of CPR, but in real life, resuscitation during pre-hospital care and ambulance transport is often suboptimal. Mechanical chest compression devices deliver consistent chest compressions, are not prone to fatigue and could potentially overcome some of the limitations of manual chest compression. However, there is no high-quality evidence that they improve clinical outcomes, or that they are cost effective. The Pre-hospital Randomised Assessment of a Mechanical Compression Device In Cardiac Arrest (PARAMEDIC) trial is a pragmatic cluster randomised study of the LUCAS-2 device in adult patients with non-traumatic out-of-hospital cardiac arrest. Methods The primary objective of this trial is to evaluate the effect of chest compression using LUCAS-2 on mortality at 30 days post out-of-hospital cardiac arrest, compared with manual chest compression. Secondary objectives of the study are to evaluate the effects of LUCAS-2 on survival to 12 months, cognitive and quality of life outcomes and cost-effectiveness. Methods: Ambulance service vehicles will be randomised to either manual compression (control) or LUCAS arms. Adult patients in out-of-hospital cardiac arrest, attended by a trial vehicle will be eligible for inclusion. Patients with traumatic cardiac arrest or who are pregnant will be excluded. The trial will recruit approximately 4000 patients from England, Wales and Scotland. A waiver of initial consent has been approved by the Research Ethics Committees. Consent will be sought from survivors for participation in the follow-up phase. Conclusion The trial will assess the clinical and cost effectiveness of the LUCAS-2 mechanical chest compression device. Trial Registration: The trial is registered on the International Standard Randomised Controlled Trial Number Registry (ISRCTN08233942)