Targeting lentiviral vectors to antigen-specific immunoglobulins

Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases. These pathogenic B cell Populations can be distinguished by their surface expression of monospecific immunoglobulin. Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy. We have developed an efficient rnethod to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and hi vivo. We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral Surface. This engineered vector could specifically bind to cells expressing Surface immunoglobulin recognizing CD20 (αCD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model. Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing αCD20. These results show the feasibility of engineering lentivectors to target immunoglobulin-specific cells to deliver a therapeutic effect. Such targeting lentivectors also Could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology

Refractive elastic scattering of carbon and oxygen nuclei: The mean field analysis and Airy structures

The experimental data on the $^{16}$O$+^{12}$C and $^{18}$O$+^{12}$C elastic scatterings and their optical model analysis are presented. Detailed and complete elastic angular distributions have been measured at the Strasbourg Vivitron accelerator at several energies covering the energy range between 5 and 10 MeV per nucleon. The elastic scattering angular distributions show the usual diffraction pattern and also, at larger angles, refractive effects in the form of nuclear rainbow and associated Airy structures. The optical model analysis unambiguously shows the evolution of the refractive scattering pattern. The observed structure, namely the Airy minima, can be consistently described by a nucleus-nucleus potential with a deep real part and a weakly absorptive imaginary part. The difference in absorption in the two systems is explained by an increased imaginary (mostly surface) part of the potential in the $^{18}$O$+^{12}$C system. The relation between the obtained potentials and those reported for the symmetrical $^{16}$O$+^{16}$O and $^{12}$C$+^{12}$C systems is drawn.Comment: 10 pages, 9 figures, Phys. rev. C in pres

Structure comparison of binary and weighted niche-overlap graphs

In ecological networks, niche-overlap graphs are considered as complex systems. They represent the competition between two predators that share common resources. The purpose of this paper is to investigate the structural properties of these graphs considered as weighted networks and compare their measures with the ones calculated for the binary networks. To conduct this study, we select four classical network measures : the degree of nodes, the clustering coefficient, the assortativity, and the betweenness centrality. These measures were used to analyse different type of networks such as social networks, biological networks, world wide web, etc. Interestingly, we identify significant differences between the structure of the binary and the weighted niche-overlap graphs. This study indicates that weight information reveals different features that may provide other implications on the dynamics of these networks

BIOSOLIDS USE FOR RECLAIMING FLUVIAL MINE TAILINGS

This study was conducted to determine the effect of biosolids and lime on reclamation of a heavily contaminated metal site. Within the Superfund area near Leadville, CO, biosolids and lime were amended (1998) to a 1 ha site at rates of 240 Mg per ha each. In 2006, soil samples were collected on a 10 m x 10 m grid to a depth of 30 cm across the site. Basic soil analysis included pH, EC, total C and N, inorganic and organic C, and NO3-N and NH4-N. A sequential fractionation for metal contaminants of concern (Cd, Cr, Fe, Pb, Mn, and Zn) identified associations with: 1) soluble/exchangeable; 2) specifically sorbed/weakly bound; 3) non-crystalline Fe/Mn oxides; 4) crystalline Fe/Mn oxides and organically complexed; 5) residual organic; and 6) residual inorganic phases. Sequential extraction data was cross correlated with basic soil analysis. Basic soil analysis were affected by both lime and biosolids applications. Cadmium was found primarily in mobile phases, Cu, Fe, Pb, and Mn in more resistant phases, and Zn distributed equally among all soil fractions. Metals were negatively correlated with basic soil analysis. The greatest mobile-phase metal concentrations were observed at the site’s south end. This may have been due to a lack of uniformly applied or incorporated biosolids, or not enough lime applied to raise soil pH and complex metals in more immobile phases. If mobile phases were present over the entire site prior to reclamation, then a positive phase shift has occurred towards more immobile metal phases following reclamation

Induction of Cytotoxic Oxidative Stress by d-Alanine in Brain Tumor Cells Expressing Rhodotorula gracilis d-Amino Acid Oxidase: A Cancer Gene Therapy Strategy

Overview summary Gene-directed enzyme prodrug therapy (GDEPT) is an antineoplastic treatment strategy designed to overcome the systemic toxicity of chemotherapy by specifically expressing a foreign enzyme in malignant cells that converts a nontoxic prodrug into a cytotoxic metabolite. The relative inefficiency of current in situ gene transfer methodology suggests that enzyme/prodrug combinations that produce membrane permeable metabolites will elicit a more favorable therapeutic response. Ideally, the agent produced by the transduced cell “factories” would be cytotoxic toward both proliferating and quiescent cells. We describe a novel GDEPT approach using d-amino acid oxidase from the red yeast Rhodotorula gracilis and d-alanine as a substrate that generates hydrogen peroxide, a reactive metabolite of oxygen that has both these characteristics. We also demonstrate the ability to sensitize tumor cells to this GDEPT protocol by manipulating cellular antioxidant pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63220/1/hum.1998.9.2-185.pd

Spin dynamics of wave packets evolving with the Dirac Hamiltonian in atoms with high Z

The motion of circular WP for one electron in central Coulomb field with high Z is calculated. The WP is defined in terms of solutions of the Dirac equation in order to take into account all possible relevant effects in particular the spin-orbit potential. A time scale is defined within which spin dynamics must be taken into account mainly in the atoms with high Z. Within this time scale there exists a mechanism of collapses and revivals of the spin already shown by the authors for harmonic oscillator potential and called the 'spin-orbit pendulum'. However this effect has not the exact periodicity of the simpler model, but the WP's spatial motion is nevertheless quite similar.Comment: 17 pages, 9 figures, LaTeX2e, uses IOP style files (included). Title changed, one reference adde

How Unpopular Policies are Made: Examples from South Africa, Singapore, and Bangladesh

In this article we contribute to the emerging knowledge on migration policy?making in two ways. Firstly, we address the relative lack of research on the gendered nature of migration policy?making. Secondly we contribute to understanding migration policymaking in postcolonial contexts. Based on case studies from Bangladesh, South Africa, and Singapore, we trace the drivers of policy change in these contexts and how the gendered vulnerability of the intended beneficiaries impacted the policy process. We found that there were four main drivers of migration policy?making in each of the countries. They were: the role?players in the policy change process, the debates that shaped the policy change, the research involved, and the political context in which the policy change took place. While our research drew on existing policy frameworks, it also showed that policy development is shaped by complex socio?political conditions.DFIDMigrating out of Povert

Modified gravity without dark matter

On an empirical level, the most successful alternative to dark matter in bound gravitational systems is the modified Newtonian dynamics, or MOND, proposed by Milgrom. Here I discuss the attempts to formulate MOND as a modification of General Relativity. I begin with a summary of the phenomenological successes of MOND and then discuss the various covariant theories that have been proposed as a basis for the idea. I show why these proposals have led inevitably to a multi-field theory. I describe in some detail TeVeS, the tensor-vector-scalar theory proposed by Bekenstein, and discuss its successes and shortcomings. This lecture is primarily pedagogical and directed to those with some, but not a deep, background in General RelativityComment: 28 pages, 10 figures, lecture given at Third Aegean Summer School, The Invisible Universe: Dark Matter and Dark Energy, minor errors corrected, references update