Water and the Biology of Prions and Plaques

This is an attempt to account for the insolubility and/or aggregation of prions and plaques in terms of a model of water consisting of an equilibrium between high 
density and low density microdomains. Hydrophobic molecules, including proteins, 
accumulate selectively into stable populations, enriched in high density water, at 
charged sites on biopolymers. In enriched high density water, proteins are probably 
partially unfolded and may precipitate out when released. All extracellular matrices 
contain such charged polymers. Prions, which have been shown to accumulate in soils 
and clays containing silicates and aluminates also probably accumulate in 
extracellular matrices. 
 
Release of proteins follows hydrolysis of the charged groups by highly reactive high 
density water. This is normally a slow process but is greatly accelerated by urea. 
Plaques may form with age and disease because of accumulation of urea and, perhaps, 
glucose in the blood. This favours precipitation of proteins emerging from matrices, 
rather than refolding and solution. Dialysis should, therefore, interfere with plaque 
formation and impede the development of some age-related diseases

Some Empirical Criteria for Attributing Creativity to a Computer Program

Peer reviewedPostprin

Hydrodynamic induced deformation and orientation of a microscopic elastic filament

We describe simulations of a microscopic elastic filament immersed in a fluid and subject to a uniform external force. Our method accounts for the hydrodynamic coupling between the flow generated by the filament and the friction force it experiences. While models that neglect this coupling predict a drift in a straight configuration, our findings are very different. Notably, a force with a component perpendicular to the filament axis induces bending and perpendicular alignment. Moreover, with increasing force we observe four shape regimes, ranging from slight distortion to a state of tumbling motion that lacks a steady state. We also identify the appearance of marginally stable structures. Both the instability of these shapes and the observed alignment can be explained by the combined action of induced bending and non-local hydrodynamic interactions. Most of these effects should be experimentally relevant for stiff micro-filaments, such as microtubules.Comment: three figures. To appear in Phys Rev Let

In Situ Characterisation of Permanent Magnetic Quadrupoles for focussing proton beams

High intensity laser driven proton beams are at present receiving much attention. The reasons for this are many but high on the list is the potential to produce compact accelerators. However two of the limitations of this technology is that unlike conventional nuclear RF accelerators lasers produce diverging beams with an exponential energy distribution. A number of different approaches have been attempted to monochromise these beams but it has become obvious that magnetic spectrometer technology developed over many years by nuclear physicists to transport and focus proton beams could play an important role for this purpose. This paper deals with the design and characterisation of a magnetic quadrupole system which will attempt to focus and transport laser-accelerated proton beams.Comment: 20 pages, 42 figure

Effectiveness of a social support intervention on infant feeding practices : randomised controlled trial

Background: To assess whether monthly home visits from trained volunteers could improve infant feeding practices at age 12 months, a randomised controlled trial was carried out in two disadvantaged inner city London boroughs. Methods: Women attending baby clinics with their infants (312) were randomised to receive monthly home visits from trained volunteers over a 9-month period (intervention group) or standard professional care only (control group). The primary outcome was vitamin C intakes from fruit. Secondary outcomes included selected macro and micro-nutrients, infant feeding habits, supine length and weight. Data were collected at baseline when infants were aged approximately 10 weeks, and subsequently when the child was 12 and 18 months old. Results: Two-hundred and twelve women (68%) completed the trial. At both follow-up points no significant differences were found between the groups for vitamin C intakes from fruit or other nutrients. At first follow-up, however, infants in the intervention group were significantly less likely to be given goats’ or soya milks, and were more likely to have three solid meals per day. At the second follow-up, intervention group children were significantly less likely to be still using a bottle. At both follow-up points, intervention group children also consumed significantly more specific fruit and vegetables. Conclusions: Home visits from trained volunteers had no significant effect on nutrient intakes but did promote some other recommended infant feeding practices

Regression of murine lung tumors by the let-7 microRNA.

MicroRNAs (miRNAs) have recently emerged as an important new class of cellular regulators that control various cellular processes and are implicated in human diseases, including cancer. Here, we show that loss of let-7 function enhances lung tumor formation in vivo, strongly supporting the hypothesis that let-7 is a tumor suppressor. Moreover, we report that exogenous delivery of let-7 to established tumors in mouse models of non-small-cell lung cancer (NSCLC) significantly reduces the tumor burden. These results demonstrate the therapeutic potential of let-7 in NSCLC and point to miRNA replacement therapy as a promising approach in cancer treatment

Dynamical epidemic suppression using stochastic prediction and control

We consider the effects of noise on a model of epidemic outbreaks, where the outbreaks appear. randomly. Using a constructive transition approach that predicts large outbreaks, prior to their occurrence, we derive an adaptive control. scheme that prevents large outbreaks from occurring. The theory inapplicable to a wide range of stochastic processes with underlying deterministic structure.Comment: 14 pages, 6 figure

Tidal Interaction between a Fluid Star and a Kerr Black Hole in Circular Orbit

We present a semi-analytic study of the equilibrium models of close binary systems containing a fluid star (mass $m$ and radius $R_0$) and a Kerr black hole (mass $M$) in circular orbit. We consider the limit $M\gg m$ where spacetime is described by the Kerr metric. The tidally deformed star is approximated by an ellipsoid, and satisfies the polytropic equation of state. The models also include fluid motion in the stellar interior, allowing binary models with nonsynchronized stellar spin (as expected for coalescing neutron star-black hole binaries) to be constructed. Tidal disruption occurs at orbital radius $r_{\rm tide}\sim R_0(M/m)^{1/3}$, but the dimensionless ratio $\hat r_{\rm tide}=r_{\rm tide}/[R_0(M/m)^{1/3}]$ depends on the spin parameter of the black hole as well as on the equation of state and the internal rotation of the star. We find that the general relativistic tidal field disrupts the star at a larger $\hat r_{\rm tide}$ than the Newtonian tide; the difference is particularly prominent if the disruption occurs in the vicinity of the black hole's horizon. In general, $\hat r_{\rm tide}$ is smaller for a (prograde rotating) Kerr black hole than for a Schwarzschild black hole. We apply our results to coalescing black hole-neutron star and black hole-white dwarf binaries. The tidal disruption limit is important for characterizing the expected gravitational wave signals and is relevant for determining the energetics of gamma ray bursts which may result from such disruption.Comment: 29 pages including 8 figures. Minor changes and update. To appear in ApJ, March 20, 2000 (Vol.532, #1