Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

Mesoscopic Superconducting Disc with Short-Range Columnar Defects

Short-range columnar defects essentially influence the magnetic properties of a mesoscopic superconducting disc.They help the penetration of vortices into the sample, thereby decrease the sample magnetization and reduce the upper critical field. Even the presence of weak defects split a giant vortex state (usually appearing in a clean disc in the vicinity of the transition to a normal state) into a number of vortices with smaller topological charges. In a disc with a sufficient number of strong enough defects vortices are always placed onto defects. The presence of defects lead to the appearance of additional magnetization jumps related to the redistribution of vortices which are already present on the defects and not to the penetration of new vortices.Comment: 14 pgs. RevTex, typos and figures corrected. Submitted to Phys. Rev.

Magnetoresistance of a 2-dimensional electron gas in a random magnetic field

We report magnetoresistance measurements on a two-dimensional electron gas (2DEG) made from a high mobility GaAs/AlGaAs heterostructure, where the externally applied magnetic field was expelled from regions of the semiconductor by means of superconducting lead grains randomly distributed on the surface of the sample. A theoretical explanation in excellent agreement with the experiment is given within the framework of the semiclassical Boltzmann equation.Comment: REVTEX 3.0, 11 pages, 3 Postscript figures appended. The manuscript can also be obtained from our World Wide Web server: http://roemer.fys.ku.dk/randmag.ht

Calculation of releases of radioactive materials in gaseous and liquid effluents from boiling water reactors (BWR-GALE Code)

The calculational procedures described in the report reflect current NRC staff practice. The methods described will be used in the evaluation of applications for construction permits and operating licenses docketed after January 1, 1979, until this NUREG is revised as a result of additional staff review. The BWR-GALE (Boiling Water Reactor Gaseous and Liquid Effluents) Code is a computerized mathematical model for calculating the release of radioactive material in gaseous and liquid effluents from boiling water reactors (BWRs). The calculations are based on data generated from operating reactors, field tests, laboratory tests, and plant-specific design considerations incorporated to reduce the quantity of radioactive materials that may be released to the environment

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Geographically touring the eastern bloc: British geography, travel cultures and the Cold War

This paper considers the role of travel in the generation of geographical knowledge of the eastern bloc by British geographers. Based on oral history and surveys of published work, the paper examines the roles of three kinds of travel experience: individual private travels, tours via state tourist agencies, and tours by academic delegations. Examples are drawn from across the eastern bloc, including the USSR, Poland, Romania, East Germany and Albania. The relationship between travel and publication is addressed, notably within textbooks, and in the Geographical Magazine. The study argues for the extension of accounts of cultures of geographical travel, and seeks to supplement the existing historiography of Cold War geography

Experiments in vortex avalanches

Avalanche dynamics is found in many phenomena spanning from earthquakes to the evolution of species. It can be also found in vortex matter when a type II superconductor is externally driven, for example, by increasing the magnetic field. Vortex avalanches associated with thermal instabilities can be an undesirable effect for applications, but "dynamically driven" avalanches emerging from the competition between intervortex interactions and quenched disorder constitute an interesting scenario to test theoretical ideas related with non-equilibrium dynamics. However, differently from the equilibrium phases of vortex matter in type II superconductors, the study of the corresponding dynamical phases - in which avalanches can play a role - is still in its infancy. In this paper we critically review relevant experiments performed in the last decade or so, emphasizing the ability of different experimental techniques to establish the nature and statistical properties of the observed avalanche behavior.Comment: To be published in Reviews of Modern Physics April 2004. 17 page

ELL’s science meaning making in multimodal inquiry: a case-study in a Hong Kong bilingual school

This paper reports on a multimodal teaching approach delivered to grade 5 elementary students in a bilingual school in Hong Kong, as part of a larger research study aimed at supporting English Language Learners (ELLs) in science class. As language demands of reading, writing and talking science place additional challenges on ELLs, there is much research interest in exploring the use of multiple modes of communication beyond the dominant use of verbal and written language. Research has shown that students develop a better scientific understanding of natural phenomena by using and alternating between a variety of representations. Yet, questions remain as to what meanings ELLs make during a multimodal discourse and, in turn, how such discourse provides support to ELLs in learning science. Drawing on social semiotics, which theorizes language as a meaning making resource comprising a range of modes (e.g. gestures and diagrams), we used a case-study approach to examine how a multimodal instructional approach provided 10 students with multiple avenues to make sense of science learning. Video recordings (capturing gestures, speech and model manipulation) and student works (drawing and writing) were collected during nine inquiry science lessons, which encompassed biology, physics and chemistry science units. Multimodal transcription allowed discourse to be analysed at a fine-grain level which, together with analysis of student works, indicated that the multimodal instructional approach provided the necessary inquiry opportunities and variety of language experiences for ELLs to build science understandings. Analysis also revealed how the affordances of modes attributed to the meaning making potentials for the ELLs and how they provided alternate communication avenues in which new meanings could be made. The findings from this study have implications for ELLs learning science within the growing multilingual Asia-Pacific region