In vitro inhibition of HIV-1 by Met-SDF-1β alone or in combination with antiretroviral drugs

Compounds that can block the CXCR4 chemokine receptor are a promising new class of antiretroviral agents. In these experiments we studied the effect of a modified form of the native stromal cell-derived factor- 1 (SDF-1), Met-SDF-1\u3b2. The in vitro susceptibility of two different CXCR4-tropic HIV-1 strains was determined. Antiviral effect was assessed by the reduction of p24 antigen production in PHA-stimulated peripheral blood mononuclear cells with exposure to the modified SDF-1 molecule. The 50% inhibitory concentrations (IC50) were derived from six separate experiments. The IC50 against the two HIV-1 isolates was in 1.0-2.8 \u3bcg/ml range for Met-SDF-1\u3b2. Met-SDF-1\u3b2 showed synergy to additivity with either zidovudine or nelfinavir at IC75, IC90 and IC95. Additivity was seen when Met-SDF-1\u3b2 was combined with efavirenz. No cellular toxicity was observed at the highest concentrations when these agents were used either singly or in combination. This compound is a promising new candidate in a receptor-based approach to HIV-1 infection in conjunction with currently available combination antiretroviral drug therapies

Learning from multimedia and hypermedia

Computer-based multimedia and hypermedia resources (e.g., the world wide web) have become one of the primary sources of academic information for a majority of pupils and students. In line with this expansion in the field of education, the scientific study of learning from multimedia and hypermedia has become a very active field of research. In this chapter we provide a short overview with regard to research on learning with multimedia and hypermedia. In two review sections, we describe the educational benefits of multiple representations and of learner control, as these are the two defining characteristics of hypermedia. In a third review section we describe recent scientific trends in the field of multimedia/hypermedia learning. In all three review sections we will point to relevant European work on multimedia/hypermedia carried out within the last 5 years, and often carried out within the Kaleidoscope Network of Excellence. According to the interdisciplinary nature of the field this work might come not only from psychology, but also from technology or pedagogy. Comparing the different research activities on multimedia and hypermedia that have dominated the international scientific discourse in the last decade reveals some important differences. Most important, a gap seems to exist between researchers mainly interested in a “serious” educational use of multimedia/ hypermedia and researchers mainly interested in “serious” experimental research on learning with multimedia/hypermedia. Recent discussions about the pros and cons of “design-based research” or “use-inspired basic research” can be seen as a direct consequence of an increasing awareness of the tensions within these two different cultures of research on education

The Sticking and Dissociation of . . .

The kinetics of the adsorption of NH 3 on W(110) and its subsequent dissociation have been investigated using molecular beam techniques and temperature programmed desorption (TPD) for surface temperatures ranging from 140 to 700 K. NH 3 shows a wide desorption peak around 270 K and a smaller peak at 170 K while H 2 and N 2 , produced by dissociation, desorbed at 550 K and 1350 K, respectively, with kinetic parameters similar to those reported for H and N generated by adsorption of H 2 and N 2 . At normal incidence and for a surface temperature of 140 K, the NH 3 sticking coefficient was found to decrease from unity at a beam energy of 0.8 kcal/mol to 0.5 for a beam energy of 5.4 kcal/mol. The sticking coefficient generally decreases with surface temperature to a value of 0.05 at 700 K, but, for a 5.4 kcal/mol beam, it exhibits a relative minimum near 300 K. The reflection coefficient of NH 3 , for an angle of incidence of 49, increases with temperature and incident beam energy in agreement with the sticking measurements. The TPD peak positions, sticking and reflection data are all well reproduced by a three-state model based on simple kinetics

In vitro inhibition of HIV-1 by Met-SDF-1beta alone or in combination with antiretroviral drugs

Compounds that can block the CXCR4 chemokine receptor are a promising new class of antiretroviral agents. In these experiments we studied the effect of a modified form of the native stromal cell-derived factor-1 (SDF-1), Met-SDF-1beta. The in vitro susceptibility of two different CXCR4-tropic HIV-1 strains was determined. Antiviral effect was assessed by the reduction of p24 antigen production in PHA-stimulated peripheral blood mononuclear cells with exposure to the modified SDF-1 molecule. The 50% inhibitory concentrations (IC50) were derived from six separate experiments. The IC50 against the two HIV-1 isolates was in 1.0-2.8 microg/ml range for Met-SDF-1beta. Met-SDF-1beta showed synergy to additivity with either zidovudine or nelfinavir at IC75 IC90 and IC95. Additivity was seen when Met-SDF-1beta was combined with efavirenz. No cellular toxicity was observed at the highest concentrations when these agents were used either singly or in combination. This compound is a promising new candidate in a receptor-based approach to HIV-1 infection in conjunction with currently available combination antiretroviral drug therapies