High-resolution studies of lung surfactant collapse

Survanta is a replacement lung surfactant (LS) used in the treatment of respiratory distress syndrome (RDS), the fourth leading cause of infant mortality in the United States. It consists of purified LS from bovine sources and retains the surfactant proteins (SP) SP-B and SP-C, both thought to be important in proper respiratory function. As such, it provides a useful and biologically relevant model system to probe the structure and function of natural LS. Here, we report results from high-resolution studies on model monolayers formed from Survanta to probe the mechanism of collapse at high surface pressure. Our results show the formation of two different collapse structures. At 62 mN/m, slightly below the collapse pressure, monolayer collapse occurs through buckling. Confocal fluorescence measurements on supported films reveal regions of overlapping phase structure in the films that mark the transition from monolayer to multilayer. Simultaneous near-field scanning optical microscopy fluorescence and force measurements show that the transition seen in the fluorescence measurements accompanies corresponding approximately 4-5 nm changes in membrane topography. This change in height is consistent with bilayer formation on monolayer collapse. Analysis of the phase structure near the transitions also suggests that the buckling occurs from a continuous film. However, when the film is compressed to its collapse pressure of 65 mN/m, buckling is no longer evident in the collapsed region. In addition, multilayers and lipid-protein aggregates that are up to 40 nm higher than the monolayer are observed in the collapsed film at this pressure.     

Selective dispersion of single-walled carbon nanotubes in the presence of polymers: the role of molecular and colloidal length scales

Dimensionality is known to play a key role in the solution behavior of nano- and mesoparticles. In particular, the shape and the range of the attractive van der Waals interparticle potential are determined by the number of microscopic versus mesoscopic dimensions. For single-walled nanotubes (SWNTs), where two of the dimensions are nanoscopic and one is mesoscopic, the intertube attraction is relatively short ranged, albeit very steep. The very large attraction (compared to the thermal energy, K(b)T) among long SWNTs leads to aggregation at different levels and constitutes a major barrier for manipulation and utilization of SWNTs. This study demonstrates that it is possible to shape the intertube potential by decorating SWNTs with end-tethered polymers. In good solvent conditions for the polymers, entropic repulsion among the tethered chains generates a free energy barrier that prevents SWNTs from approaching the attractive part of the intertube potential. Consequentially, stable dispersions of individual, well separated SWNTs can be prepared. Investigation of different chain lengths and tethering densities of the polymers as well as the interparticle potentials for nanometric versus mesoscopic particles suggests that polymer-induced steric stabilization provides a generic method for separation of SWNTs from mixtures of colloidal species, as demonstrated experimentally.     

High affinity, paralog-specific recognition of the Mena EVH1 domain by a miniature protein

Many protein domains involved in cell signaling contain or interact with proline-rich sequences, and the design of molecules that perturb signaling pathways represents a foremost goal of chemical biology. Previously we described a protein design strategy in which the well-folded alpha-helix in avian pancreatic polypeptide (aPP) presents short alpha-helical recognition epitopes. The miniature proteins designed in this way recognize even shallow protein clefts with high affinity and specificity. Here we show that the well-folded type-II polyproline helix in aPP can present the short PPII-helical recognition epitope within the ActA protein of Listeria monocytogenes. Like miniature proteins that use an alpha-helix for protein recognition, the miniature protein designed in this way displays high affinity for a natural ActA target, the EVH1 domain Mena1-112, and achieves the elusive goal of paralog specificity, discriminating well between EVH1 domains Mena1-112, VASP1-115, and Evl1-112. Most importantly, the miniature protein competed with ActA in Xenopus laevis egg cytoplasmic extracts, decreasing actin-dependent motility of L. monocytogenes and causing extreme speed variations and discontinuous tail formation. Our results suggest that miniature proteins based on aPP may represent an excellent framework for the design of ligands that differentiate the roles of EVH1 domains in vitro and in vivo.     

NMR in rotating magnetic fields: magic-angle field spinning

Magic-angle sample spinning is one of the cornerstones in high-resolution NMR of solid and semisolid materials. The technique enhances spectral resolution by averaging away rank 2 anisotropic spin interactions, thereby producing isotropic-like spectra with resolved chemical shifts and scalar couplings. In principle, it should be possible to induce similar effects in a static sample if the direction of the magnetic field is varied (e.g., magic-angle rotation of the B0 field). Here we will review some recent experimental results that show progress toward this goal. Also, we will explore some alternative approaches that may enable the recovery of spectral resolution in cases where the field is rotating off the magic angle. Such a possibility could help mitigate the technical problems that render difficult the practical implementation of this method at moderately strong magnetic fields.     

Chirp-induced dynamics of femtosecond filaments in air

We investigate the influence of a chirped phase on femtosecond pulses propagating in air. Pulses with an initially negative chirp are temporally compressed by compensation with group-velocity dispersion. We demonstrate that this property, combined with plasma defocusing, can be used to trigger filamentation at different foci, increase self-guiding ranges, or even shorten pulse duration.     

Rigidity,reduction, and ramification

In this paper we consider wildly ramified G-Galois covers of curves f:Y¹_k branched at exactly one point over an algebraically closed field k of characteristic p. For G equal to A_p or PSL₂(p), we prove Abhyankar's Inertia Conjecture that all possible inertia groups occur over infinity for such covers f. In addition, we prove that the set of conductors that can be realized depends on the group. The method we use is to compute the reduction of Galois covers of branched at 3 points. We observe that the existence of covers with given inertia in characteristic p is closely related to the arithmetic of covers in characteristic zero.Mathematics Subject Classification (2000): 14H30, 14G32     

Public attitudes to human gene therapy: a pilot study in Wales

OBJECTIVE: This study aimed to explore some factors influencing perceptions of human gene therapy. METHOD: A small qualitative study using two semi-structured interviews per participant (n = 22). The groups comprised (1) people with cystic fibrosis and members of their family (n = 9), and (2) students from a science evening class as well as lay members of the public selected from the practice list of a local general practitioner (n = 13). RESULTS: This pilot study demonstrates support for somatic gene therapy and ambivalence about germline gene therapy. A clear distinction is drawn between therapy and enhancement, with the majority opposing gene enhancement. CONCLUSIONS: Attitudes towards the acceptability of gene therapy are not necessarily determined by experience of, or exposure to, a genetic condition. More research is needed with the general public to determine what is perceived to be acceptable public policy in this field.     

Taut foliations in punctured surface bundles, I

Given a fibred, compact, orientable 3-manifold with single boundarycomponent, we show that a fibration with fiber surface of negativeEuler characteristic can be perturbed to yield taut foliationsrealizing an open interval of boundary slopes about the boundaryslope of the fibration. These taut foliations extend to tautfoliations in the corresponding surgery manifolds. 2000 MathematicsSubject Classification: primary 57M25; secondary 57R30.