In-utero transplantation of parental CD34 haematopoietic progenitor cells in a patient with X-linked severe combined immunodeficiency (SCIDXI)

BACKGROUND: X-linked severe combined immunodeficiency (SCIDXI) is an inherited immune defect which leads to death in infancy from severe infections. The defect is caused by mutations of the IL-2RG gene that encodes for the common gamma chain shared by several cytokine receptors. The disease is characterised by lack of T and NK cells with normal numbers of B cells. SCIDXI can be cured by bone marrow transplantation (BMT) or prevented by abortion after prenatal diagnosis. METHODS: A male fetus was diagnosed as having SCIDXI by molecular, immunophenotypic, and functional analyses. The fetus was injected intraperitoneally under ultrasound guidance with CD34 haematopoietic progenitor cells purified from paternal bone marrow and T-cell depleted by E rosetting. Chimerism analysis was by HLA-DQ alpha typing and gamma-chain staining on cord blood. FINDINGS: A healthy 3.6 kg boy was delivered by caesarean section at 38 weeks of gestation with no clinical or laboratory signs of graft-versus-host disease. Engraftment of donor-derived CD2 cells was found at birth. At 3.5 months of age the infant is well and his T-cell counts and function are normal. INTERPRETATION: In-utero transplantation of haematopoietic progenitor cells allowed immune reconstitution of a fetus with SCIDXI and may be an alternative to elective abortion. Our report should encourage applications of this method to other inherited disorders curable by BMT.     

Modelling diffusion-controlled kinetics in equilibrium and driven alloys

Summary We introduce a very simple model for thermally activated atomic migration on a lattice, and several techniques to handle it. For thermodynamical systems, the model can be used for simulating decomposition paths taking into account relevant metallurgical features. Close to equilibrium, the simplest mean-field approximation of the model can be linearized with respect to the departure from equilibrium; one then gets a microscopic interpretation of classical phenomenological coefficients, such as mobility, interfacial transfer coefficient, rate constants for the coupled relaxation of concentration and order fields. Further away from the equilibrium, the nonlinearities can be taken into account in a consistent way. For driven alloys, i.e. alloys submitted to external forcing, forced atomic migration is added to the model and new features emerge: the model is supported by several experimental results some of which confirmed its predictions a posteriori.     

A model for the seismic reliability assessment of electric power transmission systems

A comprehensive model to evaluate the seismic reliability of electric power transmission systems is presented. The model provides information on the probability of structural failure of critical equipment at the major substations, from which the corresponding probabilities of power disruption to a given service area are determined. With the proposed methodology earthquake ground motions are defined as stochastic processes, and seismic capacities of electrical equipment are determined on the basis of available test data and simple modeling, from which fragility functions of critical equipment and specific substations are developed. Probabilities of power disruption resulting from network disconnectivity and abnormal power flow are assessed through Monte Carlo simulation. As a case study, the proposed model is applied to the electric power network in San Francisco and vicinity under the 1989 Loma Prieta earthquake, and the probabilities of power interruption are contrasted with the actual power failures observed during that earthquake.     

Digital implementation of bus clamped space vector modulation

Space vector modulation has recently become a popular PWM method of supplying a high performance drive. An adaptation of SVM modulation is presented here. This system is called bus clamped space vector modulation. This method has some practical advantages when compared to normal SVM. These include a reduced average switching frequency, easy digital implementation and asynchronous control and switching frequencies     

Frequency-dependence of myocardial energetics in failing human myocardium as quantified by a new method for the measurement of oxygen consumption in muscle strip preparations

Diastolic dysfunction at high heart rates may be associated with increased myocardial energy consumption. Frequency-dependent changes of isometric force and oxygen consumption (MVO2) were investigated in strip preparations from endstage failing human hearts exhibiting various degrees of diastolic dysfunction. MVO2 was determined by a new method which was validated. When stimulation rate was increased from 40 to 200 min-1 (n=7), developed force decreased from 16.5+/-4.3 to 7.9+/-2.9 mN/mm2 (P<0.01), diastolic force increased from 15.9+/-3.2 to 22.0+/-3.0 mN/mm2 (P<0.01), and total MVO2 increased from 2.6+/-0.6 to 4.7+/-0.9 ml/min/100 g (P<0.025). Resting MVO2 and resting force were 1.8+/-0.4 ml/min/100 g and 15.9+/-3.0 mN/mm2, respectively. After addition of 30 mm 2,3-butanedione monoxime (BDM) to inhibit crossbridges, resting MVO2 and resting force decreased by 46% (P<0.05) and 15% (P<0.01), respectively, indicating the presence of active force generation in unstimulated failing human myocardium. In each muscle preparation, there was a significant correlation between force-time integral (FTI) and total MVO2 (r=0.96+/-0.01). The strength of these correlations did not vary with the contribution of diastolic FTI to total FTI. The ratio of activity related MVO2 to developed FTI, an inverse index of the economy of contraction, increased depending on the rise of diastolic FTI at higher stimulation rates. In conclusion, in failing human myocardium, diastolic force development is occurring at the same energy expenditure as systolic force generation. Therefore, in muscle preparations with disturbed diastolic function economy of contraction decreases with higher stimulation rates, depending on the rise of diastolic force.     

The use of sodium thiocyanate for the salting-out of water-soluble dyes

During a recent attempt to produce solid forms of water-soluble, sulphonated reactive dye samples with low electrolyte content, it was found that salting-out of such dyes with sodium thiocyanate dihydrate and subsequent washing with acetone gave a product with very low content of inorganic salts. A readily soluble solid of high tinctorial strength was produced.