1,281 research outputs found
Computational information geometry in statistics: foundations
This paper lays the foundations for a new framework for numerically and computationally applying information geometric methods to statistical modelling
Molecular interconversion behaviour in comprehensive two-dimensional gas chromatography
Comprehensive two-dimensional gas chromatography (GC x GC) is shown to provide information on dynamic molecular behaviour (interconversion), with the interconversion process occurring on both columns in the coupled-column experiment. The experiment requires suitable adjustment of both experimental conditions and relative dimensions of each of the columns. In this case, a longer column than normally employed in GC x GC allows sufficient retention duration on the second column, which permits the typical plateau-shape recognised for the interconversion process to be observed. The extent of interconversion depends on prevailing temperature, retention time, and the phase type. Polyethylene glycol-based phases were found to result in high interconversion kinetics, although terephthalic acid-terminated polyethylene glycol had a lesser extent of interconversion. Much less interconversion was seen for phenyl-methylpolysiloxane and cyclodextrin phases. This suggests that for the oximes, interconversion largely occurs in the stationary phase. Examples of different extents of interconversion in both dimensions are shown, including peak coalescence on the first column with little interconversion on the second column
An assertion language for constraint logic programs
In an advanced program development environment, such as that discussed in the introduction of this book, several tools may coexist which handle both the program and information on the program in different ways. Also, these tools may interact among themselves and with the user. Thus, the different tools and the user need some way to communicate. It is our design principie that such communication be performed in terms of assertions. Assertions are syntactic objects which allow expressing properties of programs. Several assertion languages have been used in the past in different contexts, mainly related to program debugging. In this chapter we propose a general language of assertions which is used in different tools for validation and debugging of constraint logic programs in the context of the DiSCiPl project. The assertion language proposed is parametric w.r.t. the particular constraint domain and properties of interest being used in each different tool. The language proposed is quite general in that it poses few restrictions on the kind of properties which may be expressed. We believe the assertion language we propose is of practical relevance and appropriate for the different uses required in the tools considered
Automatically Discovering Hidden Transformation Chaining Constraints
Model transformations operate on models conforming to precisely defined
metamodels. Consequently, it often seems relatively easy to chain them: the
output of a transformation may be given as input to a second one if metamodels
match. However, this simple rule has some obvious limitations. For instance, a
transformation may only use a subset of a metamodel. Therefore, chaining
transformations appropriately requires more information. We present here an
approach that automatically discovers more detailed information about actual
chaining constraints by statically analyzing transformations. The objective is
to provide developers who decide to chain transformations with more data on
which to base their choices. This approach has been successfully applied to the
case of a library of endogenous transformations. They all have the same source
and target metamodel but have some hidden chaining constraints. In such a case,
the simple metamodel matching rule given above does not provide any useful
information
A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci
The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function
Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established
Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI) influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus) and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 Β΅g 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1). Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes
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