Molecular dynamics study of water channels in natural and synthetic amyloid-ß fibrils.

We compared all-atom explicit solvent molecular dynamics simulations of three types of Aß(1-40) fibrils: brain-seeded fibrils (2M4J, with a threefold axial symmetry) and the other two, all-synthetic fibril polymorphs (2LMN and 2LMP, made under different fibrillization conditions). Fibril models were constructed using either a finite or an infinite number of layers made using periodic images. These studies yielded four conclusions. First, finite fibrils tend to unravel in a manner reminiscent of fibril dissolution, while infinite fibrils were more stable during simulations. Second, salt bridges in these fibrils remained stable in those fibrils that contained them initially, and those without salt bridges did not develop them over the time course of the simulations. Third, all fibrils tended to develop a "stagger" or register shift of ß-strands along the fibril axis. Fourth and most importantly, the brain-seeded, 2M4J, infinite fibrils allowed bidirectional transport of water in and out of the central longitudinal core of the fibril by rapidly developing gaps at the fibril vertices. 2LMP fibrils also showed this behavior, although to a lesser extent. The diffusion of water molecules in the fibril core region involved two dynamical states: a localized state and directed diffusion in the presence of obstacles. These observations provided support for the hypothesis that Aß fibrils could act as nanotubes. At least some Aß oligomers resembled fibrils structurally in having parallel, in-register ß-sheets and a sheet-turn-sheet motif. Thus, our findings could have implications for Aß cytotoxicity, which may occur through the ability of oligomers to form abnormal water and ion channels in cell membranes.

An ethical dilemma: malignant melanoma in a 51-year-old patient awaiting simultaneous kidney and pancreas transplantation for type 1 diabetes.

Malignant melanoma is a high-risk skin cancer that, in potential transplant recipients, is considered a substantial contraindication to solid organ transplantation due to significant risk of recurrence with immunosuppression. Current guidelines stipulate waiting between 3 and 10 years after melanoma diagnosis. However, in young patients with end-stage organ failure and malignant melanoma, complex ethical and moral issues arise. Assessment of the true risk associated with transplantation in these patients is difficult due to lack of prospective data, but an autonomous patient can make a decision that clinicians may perceive to be high risk. The national and worldwide shortage of available organs also has to be incorporated into the decision to maximize the net benefit and minimize the risk of graft failure and mortality. The incidence of malignant melanoma worldwide is increasing faster than that of any other cancer and continues to pose ethically challenging decisions for transplant specialists evaluating recipients for solid organ transplantation.

Minority-spin t(2g) states and the degree of spin polarization in ferromagnetic metallic La(2-2x)Sr(1+2x)Mn(2)O(7) (x = 0.38).

A half-metal is a material with conductive electrons of one spin orientation. This type of substance has been extensively searched for due to the fascinating physics as well as the potential applications for spintronics. Ferromagnetic manganites are considered to be good candidates, though there is no conclusive evidence for this notion. Here we show that the ferromagnet La2-2xSr1+2xMn2O7 (x = 0.38) possesses minority-spin states, challenging whether any of the manganites may be true half-metals. However, when electron transport properties are taken into account on the basis of the electronic band structure, we found that the La2-2xSr1+2xMn2O7 (x = 0.38) can essentially behave like a complete half metal.

Low-energy (<10 meV) feature in the nodal electron self-energy and strong temperature dependence of the Fermi velocity in Bi{2}Sr{2}CaCu{2}O{8+δ}.

Using low photon energy angle-resolved photoemission, we study the low-energy dispersion along the nodal (π,π) direction in Bi{2}Sr{2}CaCu{2}O{8+δ} as a function of temperature. Less than 10 meV below the Fermi energy, the high-resolution data reveal a novel "kinklike" feature in the electron self-energy that is distinct from the larger well-known kink roughly 70 meV below E{F}. This new kink is strongest below the superconducting critical temperature and weakens substantially at higher temperatures. A corollary of this finding is that the Fermi velocity v{F}, as measured in this low-energy range, varies rapidly with temperature-increasing by almost 30% from 70 to 110 K. The behavior of v{F}(T) appears to shift as a function of doping, suggesting a departure from simple "universality" in the nodal Fermi velocity of cuprates.

Wrinkling and strain softening in single-wall carbon nanotube membranes.

The nonlinear elasticity of thin supported membranes assembled from length purified single-wall carbon nanotubes is analyzed through the wrinkling instability that develops under uniaxial compression. In contrast with thin polymer films, pristine nanotube membranes exhibit strong softening under finite strain associated with bond slip and network fracture. We model the response as a shift in percolation threshold generated by strain-induced nanotube alignment in accordance with theoretical predictions.

Isotopic fingerprint of electron-phonon coupling in high-Tc cuprates.

Angle-resolved photoemission spectroscopy with low-energy tunable photons along the nodal direction of oxygen isotope substituted Bi(2)Sr(2)CaCu(2)O(8+delta) reveals a distinct oxygen isotope shift near the electron-boson coupling "kink" in the electronic dispersion. The magnitude (a few meV) and direction of the kink shift are as expected due to the measured isotopic shift of phonon frequency, and are also in agreement with theoretical expectations. This demonstrates the participation of the phonons as dominant players, as well as pinpointing the most relevant of the phonon branches.

Experimental setup for low-energy laser-based angle resolved photoemission spectroscopy.

A laser-based angle resolved photoemission (ARPES) system utilizing 6 eV photons from the fourth harmonic of a mode-locked Ti:sapphire oscillator is described. This light source greatly increases the momentum resolution and photoelectron count rate, while reducing extrinsic background and surface sensitivity relative to higher energy light sources. In this review, the optical system is described, and special experimental considerations for low-energy ARPES are discussed. The calibration of the hemispherical electron analyzer for good low-energy angle-mode performance is also described. Finally, data from the heavily studied high T(c) superconductor Bi(2)Sr(2)CaCu(2)O(8+delta) (Bi2212) is compared to the results from higher photon energies.

Dielectric study of the antiplasticization of trehalose by glycerol.

Recent measurements have suggested that the antiplasticizing effect of glycerol on trehalose can significantly increase the preservation times of proteins stored in this type of preservative formulation. In order to better understand the physical origin of this phenomenon, we examine the nature of antiplasticization in trehalose-glycerol mixtures by dielectric spectroscopy. These measurements cover a broad frequency range between 40 Hz to 18 GHz (covering the secondary relaxation range of the fragile glass-former trehalose and the primary relaxation range of the strong glass-former glycerol) and a temperature (T) range bracketing room temperature (220 K to 350 K). The Havriliak-Negami function precisely fits our relaxation data and allows us to determine the temperature and composition dependence of the relaxation time tau describing a relative fast dielectric relaxation process appropriate to the characterization of antiplasticization. We observe that increasing the glycerol concentration at fixed T increases tau (i.e., the extent of antiplasticization) until a temperature dependent critical "plasticization concentration" xwp is reached. At a fixed concentration, we find a temperature at which antiplasticization first occurs upon cooling and we designate this as the "antiplasticization temperature," Tant. The ratio of the tau values for the mixture and pure trehalose is found to provide a useful measure of the extent of antiplasticization, and we explore other potential measures of antiplasticization relating to the dielectric strength.

Quasiparticlelike peaks, kinks, and electron-phonon coupling at the (pi,0) regions in the CMR oxide La2-2x Sr1+2x Mn2 O7.

Using angle-resolved photoemission, we have observed sharp quasiparticlelike peaks in the prototypical layered manganite La(2-2x)Sr(1+2x)Mn(2)O(7) (x=0.36,0.38). We focus on the (pi,0) regions of k space and study their electronic scattering rates and dispersion kinks, uncovering bilayer-split bands, the critical energy scales, momentum scales, and strengths of the interactions that renormalize the electrons. To identify these bosons, we measured phonon dispersions in the energy range of the kink by inelastic neutron scattering, finding a good match in both energy and momentum to the oxygen bond-stretching phonons.

Laser based angle-resolved photoemission, the sudden approximation, and quasiparticle-like spectral peaks in Bi2Sr2CaCu2O(8+delta).

A new low photon energy regime of angle-resolved photoemission spectroscopy is accessed with lasers and used to study the high T(C) superconductor Bi2Sr2CaCu2O(8+delta). The low energy increases bulk sensitivity, reduces background, and improves resolution. With this we observe spectral peaks which are sharp on the scale of their binding energy--the clearest evidence yet for quasiparticles in the normal state. Crucial aspects of the data such as the dispersion, superconducting gaps, and the bosonic coupling kink are found to be robust to a possible breakdown of the sudden approximation.

Wetting-dewetting transition line in thin polymer films.

Thin polymeric films are increasingly being utilized in diverse technological applications, and it is crucial to have a reliable method to characterize the stability of these films against dewetting. The parameter space that influences the dewetting of thin polymer films is wide (molecular mass, temperature, film thickness, substrate interaction) and a combinatorial method of investigation is suitable. We thus construct a combinatorial library of observations for polystyrene (PS) films cast on substrates having orthogonal temperature and surface energy gradients and perform a series of measurements for a range of molecular masses (1800 g/mol < M < 35 000 g/mol) and film thicknesses h (30 nm < h < 40 nm) to explore these primary parameter axes. We were able to obtain a near-universal scaling curve describing a wetting-dewetting transition line for polystyrene films of fixed thickness by introducing reduced temperature and surface energy variables dependent on M. Our observations also indicate that the apparent polymer surface tension gamma(p) becomes appreciably modified in thin polymer films from its bulk counterpart for films thinner than about 100-200 nm, so that bulk gamma(p) measurements cannot be used to estimate the stability of ultrathin films. Both of these observations are potentially fundamental for the control of thin film stability in applications where film dewetting can compromise film function.

Early-stage compositional segregation in polymer-blend films.

The existence of a transient period during the surface enrichment of a binary polymer blend by one of its components has been suggested by previous theoretical and experimental studies as well as computer simulations. Taking advantage of the high depth resolution of neutron reflectivity and the slow dynamics of polymers near their glass transition, we investigate this early-stage surface compositional enrichment in a phase separating polymer blend for the first time. Two stages of surface enrichment layer growth are observed. A rapid local surface enrichment at the chain segmental level occurs first, followed by a slower growth of a diffuse layer having a scale on the order of the bulk correlation length and the radius of gyration of the surface enriching polymer chains.

Incoherent neutron scattering and the dynamics of confined polycarbonate films.

Incoherent elastic neutron scattering measurements are performed on thin (75 to 1015 A) polycarbonate films supported on Si wafers. We find that the mean-square atomic displacement is diminished by thin film confinement. For film thicknesses comparable to the unperturbed dimensions of the macromolecule, we observe two characteristic crossover temperatures in as a function of temperature T, one above and the other below the bulk T(g). Furthermore, the harmonic force constant kappa, defined by the low temperature dependence of (i.e., kappa approximately k(B)T/), increases as the film thickness decreases. These observations suggest that the atoms are more strongly localized in the thin supported films.

Intrinsic viscosity and the electrical polarizability of arbitrarily shaped objects.

The problem of calculating the electric polarizability tensor alpha(e) of objects of arbitrary shape has been reformulated in terms of path integration and implemented computationally. The method simultaneously yields the electrostatic capacity C and the equilibrium charge density. These functionals of particle shape are important in many materials science applications, including the conductivity and viscosity of filled materials and suspensions. The method has been validated through comparison with exact results (for the sphere, the circular disk, touching spheres, and tori), it has been found that 10(6) trajectories yield an accuracy of about four and three significant figures for C and alpha(e), respectively. The method is fast: For simple objects, 10(6) trajectories require about 1 min on a PC. It is also versatile: Switching from one object to another is easy. Predictions have also been made for regular polygons, polyhedra, and right circular cylinders, since these shapes are important in applications and since numerical calculations of high stated accuracy are available. Finally, the path-integration method has been applied to estimate transport properties of both linear flexible polymers (random walk chains of spheres) and lattice model dendrimer molecules. This requires probing of an ensemble of objects. For linear chains, the distribution function of C and of the trace (alpha(e)), are found to be universal in a size coordinate reduced by the chain radius of gyration. For dendrimers, these distribution functions become increasingly sharp with generation number. It has been found that C and alpha(e) provide important information about the distribution of molecular size and shape and that they are important for estimating the Stokes friction and intrinsic viscosity of macromolecules.

Combinatorial study of surface pattern formation in thin block copolymer films.

Surface pattern formation in diblock copolymer films is investigated as a function of film thickness h and molecular mass M. Smooth films are observed for certain h ranges centered about multiples of the lamellar thickness L0, and we attribute this effect to an increase in the surface chain density with h in the outer brushlike copolymer layer. We also observe apparently stable labyrinthine surface patterns for other h ranges, and the average size of these patterns is found to scale as lambda approximately L0(-2.5). Hole and island patterns occur for h ranges between those of the labyrinthine patterns and the smooth regions, and their size similarly decreases with L0 and M.

Critical properties and phase separation in lattice Boltzmann fluid mixtures.

Basic equilibrium properties of lattice Boltzmann (LB) fluid mixtures (coexistence curve, surface tension, interfacial profile, correlation length) are calculated to characterize the critical phenomena occurring in these model liquids and to establish a reduced variable description allowing a comparison with real fluid mixtures. We observe mean-field critical exponents and amplitudes so that the LB model may be useful for modeling high molecular weight polymer blends and other fluid mixtures approximated over a wide temperature range by mean-field theory. We also briefly consider phase separation under quiescent and shearing conditions and point out the strong influence of interacting boundaries on the qualitative form of the late-stage phase-separation morphology.

One thousand renal transplants at Belfast City Hospital: post-graft neoplasia 1968-1999, comparing azathioprine only with cyclosporin-based regimes in a single centre.

From 1968-1999, 868 recipients of 1,000 renal transplants were followed up for neoplasia. Altogether, 102 tumours were diagnosed in 94 patients (11.8% incidence). Eighty-seven occurred among 750 single and 15 occurred among 118 multiple graft recipients. Three of 11 patients with pre-existing tumour developed posttransplant neoplasia, either new or recurrent. The most frequently seen posttransplant neoplasms were squamous carcinoma of skin, basal cell carcinoma (BCC), posttransplant lymphoproliferative disease (PTLD) and gastro-intestinal (GI) cancer. Forty-one tumour-related deaths occurred (44% mortality). Patients on CSA (C) regimes had a greater cumulative incidence of tumour after transplantation than those on azathioprine and low-dose prednisolone alone (A regime) had--12.7% (34 of 268) vs. 4.5% (15 of 335) of those at risk up to 5 years (relative increased rate of incidence 2.4) with more early cases of PTLD. C-regime patients who developed neoplasia had been prescribed significantly higher CSA doses than tumour-free controls (4.5 vs. 3.4 mg/kg/day; p = 0.014). Patients who made a late conversion from the A to the C regime subsequently developed more neoplasms than nonconverted controls (25.7% vs. 12%), mainly due to early and often aggressive squamous carcinoma. Transplant survival figures were similar for both A- and C-regime groups. These findings suggest that current CSA doses are higher than are necessary for optimal graft survival and thus increase the risk of early neoplasia without any compensatory advantage. A dose reduction of CSA to less than 3.5 mg/kg/day in long-surviving, stable graft recipients should reduce tumour risk without imperilling function. Late conversion from the A to the C regime should be avoided where possible and CSA doses in this situation kept to a minimum.

Dynamic entropy as a measure of caging and persistent particle motion in supercooled liquids.

The length-scale dependence of the dynamic entropy is studied in a molecular dynamics simulation of a binary Lennard-Jones liquid above the mode-coupling critical temperature T(c). A number of methods exist for estimating the entropy of dynamical systems, and we utilize an approximation based on calculating the mean first-passage time (MFPT) for particle displacement because of its tractability and its accessibility in real and simulation measurements. The MFPT dynamic entropy S(epsilon) is defined as equal to the inverse of the average first-passage time for a particle to exit a sphere of radius epsilon. This measure of the degree of chaotic motion allows us to identify characteristic time and space scales and to quantify the increasingly correlated particle motion and intermittency occurring in supercooled liquids. In particular, we identify a "cage" size defining the scale at which the particles are transiently localized, and we observe persistent particle motion at intermediate length scales beyond the scale where caging occurs. Furthermore, we find that the dynamic entropy at the scale of one interparticle spacing extrapolates to zero as the mode-coupling temperature T(c) is approached.