The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques

CD4+ T lymphocyte depletion in human immunodeficiency virus type 1 (HIV-1)-infected humans underlies the development of acquired immune deficiency syndrome. Using a model in which rhesus macaques were infected with chimeric simian-human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelope glycoprotein ectodomains individually contributed to the efficiency with which CD4(+) T lymphocytes were depleted. The envelope glycoproteins of recombinant SHIVs that efficiently caused loss of CD4(+) T lymphocytes exhibited increased chemokine receptor binding and membrane-fusing capacity compared with those of less pathogenic viruses. These studies identify the HIV-1 envelope glycoprotein ectodomains as determinants of CD4(+) T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms.     

Computing as compression: An overview of the SP theory and system

This article is an overview of a programme of research based on the conjecture thatall kinds of computing and formal reasoning may usefully be understood as information compression by pattern matching, unification and metrics-guided search. The research aims to develop this idea into a theory of computing to integrate and simplify diverse concepts in the field. The research also aims to develop a ‘new generation’ computing system, based on the theory, to integrate and simplify diverse kinds of computing and to achieve more flexibility and ‘intelligence’ than conventional computers. Software simulations of the proposed new system provide a concrete expression of the developing theory and a test-bed for the ideas. The background to the research is briefly reviewed including evidence that information compression is a significant element in biological information processing systems. Concepts ofinformation andredundancy are described as a basis for describing how information compression may be achieved by the comparison ormatching of patterns, the merging orunification of patterns which are the same, together withmetrics-guided search (e.g., ‘hill climbing’, ‘beam search’) to maximise compression for a given computational effort. The main elements of the SP theory and of the proposed SP system are described with a summary of developments to date. Some of the kinds of computing which be interpreted as information compression are briefly reviewed. These include: the ‘low level’ workings of conventional computers; information retrieval, pattern recognition and de-referencing of identifiers; unsupervised inductive learning (grammatical inference, data mining, automatic organisation of software and of knowledge bases); the execution of mathematical or computing functions; deductive and probabilistic inference; parsing and natural language processing; planning and problem solving. Areas of uncertainty where further work is needed are indicated at appropriate points throughout the article.     

Atypical acute dystonia

Acute dystonia is a common adverse effect following anti-psychotic medication, which mainly appears shortly after beginning treatment or increasing the dosage. Laryngeal dysfunction may carely occur as part of the picture of acute dystonia and, if so, usually with dyspnoea. We describe a case of acute dystonia with atypical onset without relation to changes in dosage and with laryngeal involvement with aphonia, but without dyspnoea.     

The role of N-glycosylation for functional expression of the human platelet-activating factor receptor. Glycosylation is required for efficient membrane trafficking

Streptococcus pneumoniae has been shown to utilize the platelet activating factor receptor for binding and invasion of host cells (Cundell, D. R., Gerard, N. P., Gerard, C., Idanpaan-Heikkila, I., and Tuomanen, E. I. (1995) Nature, in press). Because bacterial binding is in part carbohydrate dependent, and the human platelet-activating factor (PAF) receptor bears a single N-linked glycosylation sequence in the second extracellular loop, we undertook studies to determine the role of this epitope in PAF receptor function. Binding of pneumococci to COS cells transfected with the human PAF receptor is greatly reduced for a receptor mutant that bears no N-linked glycosylation site. Immunohistochemical and binding analyses show decreased expression of the non-glycosylated molecule on the cell membrane relative to the wild type receptor; however, metabolic labeling and immunopurification indicate it is synthesized intracellularly at a level similar to the native molecule. A mutant receptor encoding a functional glycosylation site at the NH2 terminus is better expressed at the cell surface compared with the non-glycosylated form, indicating that trafficking to the cell surface is facilitated by glycosylation, but its location is relatively unimportant. The binding affinity for PAF is not significantly effected by the presence or location of the carbohydrate, and variations in cell surface expression have little influence on signal transduction, as the non-glycosylated PAF receptor is equally effective for activation of phospholipase C as the native molecule. These data are supportive of pneumococcal binding on protein moiety(ies) of the PAF receptor and indicate that N-glycosylation facilitates expression of the protein on the cell membrane.     

Employment opportunities for graduates of APA-approved and non-APA-approved training programs.

Examined employers' hiring preferences and practices related to American Psychological Association (APA) approved and non-APA-approved training program graduates, based on 414 job advertisements listed in the APA Monitor and a survey of 104 employers who had advertised positions. Results indicate that employers would prefer to hire graduates of APA-approved training programs. 82% of employers in the academic area and 77% of those in the applied area reported that they would give hiring preference to APA-approved program graduates. (2 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Déplacements engendrés par des ondes élastiques incidentes sur une sphère multi-couches

In an infinite space, we study the propagation of elastic spherical waves emitted by a source point placed outside a given finite set of concentric elastic spherical layers. The exact solution (displacements fields) of this problem is determined by a new method which avoids solving the totality of equations and boundary conditions. From these results we deduce those corresponding to some particular cases.     

The Effect of Solute Content on the Slip Behavior in 7XXX Series Aluminum Alloys

The microstructures of three high strength, high purity Al-Zn-Mg-Cu alloys, in the T6 temper, were characterized extensively using quantitative optical metallography and quantitative transmission electron microscopy. Only the solute content (Mg + Zn) of these alloys was varied for this study. These alloys were shown to be identical in grain size and shape, dispersoid (E-phase) and grain boundary precipitate (ν) populations, and precipitate free zone widths. The matrix microstructures consisted of ordered GP zones and ν′ and differed only in the volume fraction of these strengthening precipitates. The higher solute alloys had the higher yield strengths and volume fractions of matrix precipitates. Subsequent slip behavior analysis of prestrained tensile specimens demonstrated that slip band spacings and slip step heights increased with increasing solute content for the same macroscopic strain (ε_p = 0.02). A work softening model by Hornbogen and Gahr was shown to predict this tendency toward increased strain localization with higher solute levels. Formerly a Research Assistant at Carnegie-Mellon University