Graphical simulation of early development of the cerebral cortex.

Much experimental data exists concerning the development of the cerebral cortex. There is a need for a common vehicle to integrate this data and to allow the testing of hypotheses concerning development. Computer simulation and visualization are powerful mechanisms for hypothesis testing. Our long-term goal is to create a robust, extensible, portable tool for simulation and visualization of cortical development to serve both research and educational purposes. This paper describes a simulation program, SimCortex, which models the early stages of development of the cerebral cortex of the mouse. Version 1.0 of SimCortex models the proliferation of progenitor cells in the pseudostratified ventricular epithelium (PVE), the generation of young neurons and their migration into the cortical plate, which is the forerunner of cell layers II through VI of the adult cortex. We present an overview of the design and implementation of SimCortex, sample output of the system and a comparison of our results with experimental data. We conclude with a brief overview of proposed future enhancements of the system.     

Human immunodeficiency virus type 1 membrane fusion mediated by a laboratory-adapted strain and a primary isolate analyzed by resonance energy transfer

Previous studies of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein-mediated membrane fusion have focused on laboratory-adapted T-lymphotropic strains of the virus. The goal of this study was to characterize membrane fusion mediated by a primary HIV-1 isolate in comparison with a laboratory-adapted strain. To this end, a new fusion assay was developed on the basis of the principle of resonance energy transfer, using HeLa cells stably transfected with gp120/gp41 from the T-lymphotropic isolate HIV-1LA1 or the macrophage-tropic primary isolate HIV-1JR-FL. These cells fused with CD4+ target cell lines with a tropism mirroring that of infection by the two viruses. Of particular note, HeLa cells expressing HIV-1JR-FL gp120/gp41 fused only with PM1 cells, a clonal derivative of HUT 78, and not with other T-cell or macrophage cell lines. These results demonstrate that the envelope glycoproteins of these strains play a major role in mediating viral tropism. Despite significant differences exhibited by HIV-1JR-FL and HIV-1LAI in terms of tropism and sensitivity to neutralization by CD4-based proteins, the present study found that membrane fusion mediated by the envelope glycoproteins of these viruses had remarkably similar properties. In particular, the degree and kinetics of membrane fusion were similar, fusion occurred at neutral pH and was dependent on the presence of divalent cations. Inhibition of HIV-1JR-FL envelope glycoprotein-mediated membrane fusion by soluble CD4 and CD4-IgG2 occurred at concentrations similar to those required to neutralize this virus. Interestingly, higher concentrations of these agents were required to inhibit HIV-1LAI envelope glycoprotein-mediated membrane fusion, in contrast to the greater sensitivity of HIV-1LAI virions to neutralization by soluble CD4 and CD4-IgG2. This finding suggests that the mechanisms of fusion inhibition and neutralization of HIV-1 are distinct.     

Effect of lung volume on lung resistance and elastance in awake subjects measured during sinusoidal forcing

BACKGROUND: Although lung volume may be changed by certain procedures during anesthesia and mechanical ventilation, dependence of the dynamic mechanical properties of the lungs on lung volume are not clear. Based on studies in dogs, the authors hypothesized that changes in lung mechanics caused by anesthesia in healthy humans could be accounted for by immediate changes in lung volume and that lung resistance will not be decreased by positive end-expiratory airway pressure if tidal volume and respiratory frequency are in the normal ranges. METHODS: Lung resistance and dynamic lung elastance were measured in six healthy, relaxed, seated subjects during sinusoidal volume oscillations at the mouth (5 mL/kg; 0.4 Hz) delivered at mean airway pressure from -9 to +25 cmH2O. Changes in lung volume from functional residual capacity were measured with inductance plethysmographic belts. RESULTS: Decreases in mean mean airway pressure that caused decreases in lung volume from functional residual capacity comparable to those typically observed during anesthesia were associated with significant increases in both dynamic lung elastance and lung resistance. Increases in mean mean airway pressure that caused increases in lung volume from functional residual capacity did not increase lung resistance and increased dynamic lung elastance only above about 15 cmH2O. CONCLUSIONS: Increases in dynamic lung elastance and lung resistance with anesthesia can be explained by the accompanying, acute decreases in lung volume, although other factors may be involved. Increasing lung volume by increasing mean airway pressure with positive end-expiratory pressure will decrease lung resistance only if the original lung volume is low compared to awake, seated functional residual capacity.     

The mysteries of multifactor ageing

Ageing of solid insulating materials and systems, according to IEC and IEEE standards, is the occurrence of irreversible deleterious changes that critically affect performance and shorten useful life. What causes ageing is not an easy question to answer, nor is it a function of an isolated event or applied stress. Years of experience have shown that the degree and rate of ageing of insulation depend on the physical and chemical properties of the material, the nature and duration of applied/induced stress(es), and material processing and treatment during manufacturing and subsequent use in equipment. Stresses that affect the integrity, reliability, and service life of electrical equipment and components, such as switchgears, transformers, and cables, include electrical, thermal, mechanical, radiation and/or environmental ones. These stresses applied sequentially or simultaneously lead to ageing and deterioration, but the rates of ageing are different and are not easily explainable     

Metal chelation and spatial profiling of components in crown ether functionalised conducting copolymer films

Crown ether functionalised conducting polymer films were used to complex barium ions from acetonitrile solution. It was found that fully-functionalised N-derivatized polypyrrole films do not possess adequate mechanical stability, but dilution with unfunctionalised bithiophene co-monomer leads to a series of copolymer films with excellent stability. Film reactivity, composition and structure were investigated using electrochemical, nanogravimetric, FTIR, XPS and neutron reflectivity techniques. The first three of these provided spatially integrated barium populations and neutron reflectivity provided spatially resolved compositional profiles. Measurements at various stages of film fabrication yielded spatial distributions of co-monomer, crown ether, solvent and barium (as perchlorate) components. Critically, the amount of free volume to accommodate crown motifs and barium within the film was limited by the film's internal microstructure and solvent content; the low solvent volume fraction creates a different local environment to solution.     

The Comparison of Four Bioluminometers and Their Swab Kits for Instant Hygiene Monitoring and Detection of Microorganisms in the Brewery

Four luminometers and their swab units were evaluated for detecting ATP by surface swabbing. Testing included pipetting known quantities of ATP directly onto the swabs; pipetting known levels of bacteria and yeast directly onto the swabs and swabbing samples of bacteria and yeast from a surface. None of these instruments and swab detection kits provided consistent, reproducible detection of ATP standards or ATP from microorganisms even at high concentrations. All of the swab kits/instruments showed poor linearity in measuring known quantities of ATP and showed high variability in ATP readings with replicate swabs containing identical concentrations of microorganisms. Since good linearity and reproducibility could be obtained using a liquid sample assay of ATP standards without swabs, it is suggested that the swab method itself may be unreliable. ATP may not be effectively released from microorganisms on swabs; ATP may adsorb to the swab interfering with detection and/or the swab might block light transmission. Swabs of bacterial/yeast suspensions dried on a sterilized surface, provided the most inconsistent ATP readings and lacked linearity. A reason for the poor detection of microbial ATP by surface swabbing could be the inability to pick up microorganisms effectively.     

For Whose Eyes Only? A Critique of the United Kingdom's Regulation of Investigatory Powers Act 2000

This article discusses the implications of the UK government's legislation designed to regulate powers of investigation with regard to the internet and new technology. The authors contend that the Regulation of Investigatory Powers Act 2000 has major ramifications for the conduct of commercial business through the internet. The authors assess the Act holistically and have placed the Act in a wider context, viewing the Act as just one facet of the UK's attempts to encourage use of the internet. The Act undoubtedly has the potential to gravely infringe upon the civil liberties of UK citizens and is a classic example of hastily drafted and ill-conceived legislation that is merely reactive and not proactive. In this regard, the Act may potentially violate the terms of the Human Rights Act 1998. Additionally, the adoption of the discredited provisions of the UK's Electronic Communications Act 2000 into the Regulation of Investigatory Powers Act is of great concern. The intention of the legislature has been to allay fears concerning the security and trustworthiness of the internet. The problem of encryption and the burden of proof is the stumbling block. The authors theorise that the opposite effect has been achieved - insecurity and doubt will increase exponentially, coupled with the attendant risk that internet companies will relocate to another jurisdiction.