Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease caused by arylsulfatase A (ARSA) deficiency. Patients with MLD exhibit progressive motor and cognitive impairment and die within a few years of symptom onset. We used a lentiviral vector to transfer a functional ARSA gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile MLD. After reinfusion of the gene-corrected HSCs, the patients showed extensive and stable ARSA gene replacement, which led to high enzyme expression throughout hematopoietic lineages and in cerebrospinal fluid. Analyses of vector integrations revealed no evidence of aberrant clonal behavior. The disease did not manifest or progress in the three patients 7 to 21 months beyond the predicted age of symptom onset. These findings indicate that extensive genetic engineering of human hematopoiesis can be achieved with lentiviral vectors and that this approach may offer therapeutic benefit for MLD patients.

No abstract

No abstract

An experimental study of Rayleigh-Be'nard convection in helium gas at roughly 5 K is performed in a cell with aspect ratio 1. Data are analysed in a ' hard turbulence ' region (4 x 10' < Ra < 6 x 10l2) in which the F'randtl number remains between 0.65 and 1.5, The main observation is a simple scaling behaviour over this entire range of Ra. However the results are not the same as in previous theories. For example, a classical result gives the dimensionless heat flux, Nu, proportional to R d while experiment gives an index much closer to 5. A new scaling theory is described. This new approach suggests scaling indices very close to the observed ones. The new approach is based upon the assumption that the boundary layer remains in existence even though its Rayleigh number is considerably greater than unity and is, in fact, diverging. A stability analysis of the boundary layer is performed which indicates that the boundary layer may be stabilized by the interaction of buoyancy driven effects and a fluctuating wind.

We introduce a lattice Boltzmann model for simulating immiscible binary fluids in two dimensions. The model, based on the Boltzmann equation of lattice-gas hydrodynamics, incorporates features of a previously introduced discrete immiscible lattice-gas model. A theoretical value of the surface-tension coefficient is derived and found to be in excellent agreement with values obtained from simulations. The model serves as a numerical method for the simulation of immiscible twophase flow; a preliminary application illustrates a simulation of flow in a two-dimensional microscopic model of a porous medium. Extension of the model to three dimensions appears straightforward.