Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.

One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA

First-principles Calculation of the Formation Energy in MgO-CaO Solid Solutions

The electronic structure and total energy were calculated for ordered and disordered MgO-CaO solid solutions within the multiple scattering theory in real space and the local density approximation. Based on the dependence of the total energy on the unit cell volume the equilibrium lattice parameter and formation energy were determined for different solution compositions. The formation energy of the solid solutions is found to be positive that is in agreement with the experimental phase diagram, which shows a miscibility gap.Comment: 11 pages, 3 figure

Time-Dependent Partition-Free Approach in Resonant Tunneling Systems

An extended Keldysh formalism, well suited to properly take into account the initial correlations, is used in order to deal with the time-dependent current response of a resonant tunneling system. We use a \textit{partition-free} approach by Cini in which the whole system is in equilibrium before an external bias is switched on. No fictitious partitions are used. Besides the steady-state responses one can also calculate physical dynamical responses. In the noninteracting case we clarify under what circumstances a steady-state current develops and compare our result with the one obtained in the partitioned scheme. We prove a Theorem of asymptotic Equivalence between the two schemes for arbitrary time-dependent disturbances. We also show that the steady-state current is independent of the history of the external perturbation (Memory Loss Theorem). In the so called wide-band limit an analytic result for the time-dependent current is obtained. In the interacting case we propose an exact non-equilibrium Green function approach based on Time Dependent Density Functional Theory. The equations are no more difficult than an ordinary Mean Field treatment. We show how the scattering-state scheme by Lang follows from our formulation. An exact formula for the steady-state current of an arbitrary interacting resonant tunneling system is obtained. As an example the time-dependent current response is calculated in the Random Phase Approximation.Comment: final version, 18 pages, 9 figure

Water solubility in aluminosilicate melts of haplogranite composition at 2 kbar

The compositional dependence of H2O solubility was investigated at 2 kbar and 800°C in haplogranite melts (system SiO2---1bNaAlSi3O8---1bKAlSi3O8 or Qz---1bAb---1bOr). The sixteen investigated compositions contained 25, 35 or 45 wt.% normative Qz and various Ab/(Ab+Or) ratios (0.15–0.92). Starting solid materials were anhydrous bubble-free glasses to which 10 wt.% H2O was added. The H2O contents of the isobarically quenched melts (glasses) were measured by Karl-Fischer titration. The results show that H2O solubility in aluminosilicate melts depends significantly upon anhydrous composition. The highest solubility values are obtained for the most Ab-rich melts. At a constant normative quartz content, the solubility of water decreases from 6.49 ± 0.20 wt.% H2O for a composition Qz35Ab60Or05 (normative composition expressed in wt.%) to 5.50 ± 0.15 wt.% H2O for a composition Qz35Ab10Or55. Along this join, the most significant changes are observed for Ab-rich melts whereas H2O solubility in Or-rich melts remains almost constant. The H2O solubility data imply that H2O is preferentially associated with the Ab component in aluminosilicate melts. Application of the results to natural granitic melts suggests that Na-rich, H2O-saturated melts may be significantly less viscous than H2O-saturated, K-rich melts. The temperature dependence of H2O solubility, investigated for composition Qz28Ab38Or34 at 2 kbar, is low. Increasing temperature from 750° to 1150°C only causes a decrease in H2O solubility from 6.00 to 5.41 wt.% H2O. These data are in agreement with previous data obtained for albite melts

Resonance Lifetimes from Complex Densities

The ab-initio calculation of resonance lifetimes of metastable anions challenges modern quantum-chemical methods. The exact lifetime of the lowest-energy resonance is encoded into a complex "density" that can be obtained via complex-coordinate scaling. We illustrate this with one-electron examples and show how the lifetime can be extracted from the complex density in much the same way as the ground-state energy of bound systems is extracted from its ground-state density

Theory of band gap bowing of disordered substitutional II-VI and III-V semiconductor alloys

For a wide class of technologically relevant compound III-V and II-VI semiconductor materials AC and BC mixed crystals (alloys) of the type A(x)B(1-x)C can be realized. As the electronic properties like the bulk band gap vary continuously with x, any band gap in between that of the pure AC and BC systems can be obtained by choosing the appropriate concentration x, granted that the respective ratio is miscible and thermodynamically stable. In most cases the band gap does not vary linearly with x, but a pronounced bowing behavior as a function of the concentration is observed. In this paper we show that the electronic properties of such A(x)B(1-x)C semiconductors and, in particular, the band gap bowing can well be described and understood starting from empirical tight binding models for the pure AC and BC systems. The electronic properties of the A(x)B(1-x)C system can be described by choosing the tight-binding parameters of the AC or BC system with probabilities x and 1-x, respectively. We demonstrate this by exact diagonalization of finite but large supercells and by means of calculations within the established coherent potential approximation (CPA). We apply this treatment to the II-VI system Cd(x)Zn(1-x)Se, to the III-V system In(x)Ga(1-x)As and to the III-nitride system Ga(x)Al(1-x)N.Comment: 14 pages, 10 figure

Density functional method for nonequilibrium electron transport

We describe an ab initio method for calculating the electronic structure, electronic transport, and forces acting on the atoms, for atomic scale systems connected to semi-infinite electrodes and with an applied voltage bias. Our method is based on the density functional theory (DFT) as implemented in the well tested Siesta approach (which uses non-local norm-conserving pseudopotentials to describe the effect of the core electrons, and linear combination of finite-range numerical atomic orbitals to describe the valence states). We fully deal with the atomistic structure of the whole system, treating both the contact and the electrodes on the same footing. The effect of the finite bias (including selfconsistency and the solution of the electrostatic problem) is taken into account using nonequilibrium Green's functions. We relate the nonequilibrium Green's function expressions to the more transparent scheme involving the scattering states. As an illustration, the method is applied to three systems where we are able to compare our results to earlier ab initio DFT calculations or experiments, and we point out differences between this method and existing schemes. The systems considered are: (1) single atom carbon wires connected to aluminum electrodes with extended or finite cross section, (2) single atom gold wires, and finally (3) large carbon nanotube systems with point defects.Comment: 18 pages, 23 figure

A Transdisciplinary Approach to Determining the Provenience of a Distorted, Pre-Columbian Skull Recovered in Rural Idaho

Transdisciplinary research involves cooperation, exchange of information, sharing of resources and integration of disciplines to achieve a common scientific goal. In this study, collaborators utilized tools and knowledge of materials science, anthropology, archaeology, geosciences and biology in an attempt to determine the provenience of skeletal remains of unknown origin. The exchange of ideas and skills along with the crossing of disciplines in this study sucessfully allowed the incorporation of expertise from many team members. This transdisciplinary approach to research provided a more comprehensive and detailed analysis than any one field alone could provide. An archaeological assessment of a human skull recovered in rural Idaho recognized cranial deformation and post-mortem application of a red pigment. A combination of scanning electron microscopy (SEM), x-ray fluorescence (XRF) and energy-dispersive x-ray spectroscopy (EDS) identified the major and trace elements present in the red post-mortem pigment as cinnabar and rare earth metals. Analysis via carbon and oxygen stable isotopes from teeth and bone to provided insight into the diet and habitat for distinct segments of the individual’s life, indicating a regional separation in early life versus late adulthood. Radiocarbon dating determined the approximate age of the skull to be between 600-700 years old and a forensic mtDNA assessmentcategorized a mitochondrial haplogroup for the remains as originating from the East African or Arabian Peninsula

Screened Coulomb interactions in metallic alloys: II Screening beyond the single-site and atomic sphere approximations

A quantitative description of the configurational part of the total energy of metallic alloys with substantial atomic size difference cannot be achieved in the atomic sphere approximation: It needs to be corrected at least for the multipole moment interactions in the Madelung part of the one-electron potential and energy. In the case of a random alloy such interactions can be accounted for only by lifting the atomic sphere and single-site approximations, in order to include the polarization due to local environment effects. Nevertheless a simple parameterization of the screened Coulomb interactions for the ordinary single-site methods, including the generalized perturbation method, is still possible. We obtained such a parameterization for bulk and surface NiPt alloys, which allows one to obtain quantitatively accurate effective interactions in this system.Comment: 24 pages, 2 figure