Evidence for the Universal Scaling Behaviour of a Freely Relaxing DNA Molecule

Relaxation measurements on a fluorescently labelled free DNA molecule after stretching by a Poiseuille flow in a capillary vessel reveal universal scaling features: at intermediate times the scaling exponent of the decay law for the molecule length as a function of time is found to be 0.51 +/- 0.05. This law is in agreement with the prediction of the Brochard-Wyart "stem and flower" model for the relaxation of a stretched polymer chain.Molecular and Cellular BiologyPhysic

Mechanism-Independent Method for Predicting Response to Multidrug Combinations in Bacteria

Drugs are commonly used in combinations larger than two for treating bacterial infection. However, it is generally impossible to infer directly from the effects of individual drugs the net effect of a multidrug combination. Here we develop a mechanism-independent method for predicting the microbial growth response to combinations of more than two drugs. Performing experiments in both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, we demonstrate that for a wide range of drugs, the bacterial responses to drug pairs are sufficient to infer the effects of larger drug combinations. To experimentally establish the broad applicability of the method, we use drug combinations comprising protein synthesis inhibitors (macrolides, aminoglycosides, tetracyclines, lincosamides, and chloramphenicol), DNA synthesis inhibitors (fluoroquinolones and quinolones), folic acid synthesis inhibitors (sulfonamides and diaminopyrimidines), cell wall synthesis inhibitors, polypeptide antibiotics, preservatives, and analgesics. Moreover, we show that the microbial responses to these drug combinations can be predicted using a simple formula that should be widely applicable in pharmacology. These findings offer a powerful, readily accessible method for the rational design of candidate therapies using combinations of more than two drugs. In addition, the accurate predictions of this framework raise the question of whether the multidrug response in bacteria obeys statistical, rather than chemical, laws for combinations larger than two.Molecular and Cellular Biolog

Torsional Directed Walks, Entropic Elasticity, and DNA Twist Stiffness

DNA and other biopolymers differ from classical polymers due to their torsional stiffness. This property changes the statistical character of their conformations under tension from a classical random walk to a problem we call the `torsional directed walk'. Motivated by a recent experiment on single lambda-DNA molecules [Strick et al., Science 271 (1996) 1835], we formulate the torsional directed walk problem and solve it analytically in the appropriate force regime. Our technique affords a direct physical determination of the microscopic twist stiffness C and twist-stretch coupling D relevant for DNA functionality. The theory quantitatively fits existing experimental data for relative extension as a function of overtwist over a wide range of applied force; fitting to the experimental data yields the numerical values C=120nm and D=50nm. Future experiments will refine these values. We also predict that the phenomenon of reduction of effective twist stiffness by bend fluctuations should be testable in future single-molecule experiments, and we give its analytic form.Comment: Plain TeX, harvmac, epsf; postscript available at http://dept.physics.upenn.edu/~nelson/index.shtm

Perturbation Theory in k-Inflation Coupled to Matter

We consider k-inflation models where the action is a non-linear function of both the inflaton and the inflaton kinetic term. We focus on a scalar-tensor extension of k-inflation coupled to matter for which we derive a modified Mukhanov-Sasaki equation for the curvature perturbation. Significant corrections to the power spectrum appear when the coupling function changes abruptly along the inflationary trajectory. This gives rise to a modification of Starobinsky's model of perturbation features. We analyse the way the power spectrum is altered in the infrared when such features are present.Comment: 20 pages, 1 figur

Near-field interactions between a subwavelength tip and a small-volume photonic-crystal nanocavity

International audienceThe fundamentals of the near-field interaction between a subwavelength metallic tip and a photonic-crystal nanocavity are investigated experimentally and theoretically. It is shown experimentally that the cavity resonance is tuned without any degradation by the presence of the tip and that the reported near-field interaction is strongly related to the field distribution within the nanostructure. Then, in light of a perturbation theory, we show that this interaction is selectively related to the electric field or magnetic field distribution within the cavity, depending on the tip properties

Syntectonic mobility of supergene nickel ores of New Caledonia (Southwest Pacific). Evidence from faulted regolith and garnierite veins.

International audienceSupergene nickel deposits of New Caledonia that have been formed in the Neogene by weathering of obducted ultramafic rocks are tightly controlled by fracture development. The relationship of tropical weathering and tectonic structures, faults and tension gashes, have been investigated in order to determine whether fractures have play a passive role only, as previously thought; or alternatively, if brittle tectonics was acting together with alteration. From the observation of time-relationship, textures, and mineralogy of various fracture fills and fault gouges, it may be unambiguously established that active faulting has play a prominent role not only in facilitating drainage and providing room for synkinematic crystallisation of supergene nickel silicate, but also in mobilising already formed sparse nickel ore, giving birth to the very high grade ore nicknamed "green gold"

Conformational spread as a mechanism for cooperativity in the bacterial flagellar switch

The bacterial flagellar switch that controls the direction of flagellar rotation during chemotaxis has a highly cooperative response. This has previously been understood in terms of the classic two-state, concerted model of allosteric regulation. Here, we used high-resolution optical microscopy to observe switching of single motors and uncover the stochastic multistate nature of the switch. Our observations are in detailed quantitative agreement with a recent general model of allosteric cooperativity that exhibits conformational spread—the stochastic growth and shrinkage of domains of adjacent subunits sharing a particular conformational state. We expect that conformational spread will be important in explaining cooperativity in other large signaling complexes

Probing complex RNA structures by mechanical force

RNA secondary structures of increasing complexity are probed combining single molecule stretching experiments and stochastic unfolding/refolding simulations. We find that force-induced unfolding pathways cannot usually be interpretated by solely invoking successive openings of native helices. Indeed, typical force-extension responses of complex RNA molecules are largely shaped by stretching-induced, long-lived intermediates including non-native helices. This is first shown for a set of generic structural motifs found in larger RNA structures, and then for Escherichia coli's 1540-base long 16S ribosomal RNA, which exhibits a surprisingly well-structured and reproducible unfolding pathway under mechanical stretching. Using out-of-equilibrium stochastic simulations, we demonstrate that these experimental results reflect the slow relaxation of RNA structural rearrangements. Hence, micromanipulations of single RNA molecules probe both their native structures and long-lived intermediates, so-called "kinetic traps", thereby capturing -at the single molecular level- the hallmark of RNA folding/unfolding dynamics.Comment: 9 pages, 9 figure

Straightening of Thermal Fluctuations in Semi-Flexible Polymers by Applied Tension

We investigate the propagation of a suddenly applied tension along a thermally excited semi-flexible polymer using analytical approximations, scaling arguments and numerical simulation. This problem is inherently non-linear. We find sub-diffusive propagation with a dynamical exponent of 1/4. By generalizing the internal elasticity, we show that tense strings exhibit qualitatively different tension profiles and propagation with an exponent of 1/2.Comment: Latex file; with three postscript figures; .ps available at http://dept.physics.upenn.edu/~nelson/pull.p