Path‐sensitive alias analysis for data flow testing

This paper describes a new approach to performing data flow testing in the presence of aliasing, and a tool based on this method. The technique is based on the observation that, under certain reasonable assumptions, one can statically determine which variables are aliased whenever control reaches a given program point via a particular path. Furthermore, one can group together paths that behave similarly with respect to aliasing and represent them by regular expressions. The resulting test requirements demand that the test data execute representatives of particular sets of paths between variable definitions and uses. Copyright © 1999 John Wiley & Sons, Ltd.     

Identification and Affinity Determination of Protein-Antibody and Protein-Aptamer Epitopes by Biosensor-Mass Spectrometry Combination

Analytical methods for molecular characterization of diagnostic or therapeutic targets have recently gained high interest. This review summarizes the combination of mass spectrometry and surface plasmon resonance (SPR) biosensor analysis for identification and affinity determination of protein interactions with antibodies and DNA-aptamers. The binding constant (K_D) of a protein–antibody complex is first determined by immobilizing an antibody or DNA-aptamer on an SPR chip. A proteolytic peptide mixture is then applied to the chip, and following removal of unbound material by washing, the epitope(s) peptide(s) are eluted and identified by MALDI-MS. The SPR-MS combination was applied to a wide range of affinity pairs. Distinct epitope peptides were identified for the cardiac biomarker myoglobin (MG) both from monoclonal and polyclonal antibodies, and binding constants determined for equine and human MG provided molecular assessment of cross immunoreactivities. Mass spectrometric epitope identifications were obtained for linear, as well as for assembled (“conformational”) antibody epitopes, e.g., for the polypeptide chemokine Interleukin-8. Immobilization using protein G substantially improved surface fixation and antibody stabilities for epitope identification and affinity determination. Moreover, epitopes were successfully determined for polyclonal antibodies from biological material, such as from patient antisera upon enzyme replacement therapy of lysosomal diseases. The SPR-MS combination was also successfully applied to identify linear and assembled epitopes for DNA–aptamer interaction complexes of the tumor diagnostic protein C-Met. In summary, the SPR-MS combination has been established as a powerful molecular tool for identification of protein interaction epitopes.     

Retail alcohol monopolies, underage drinking, and youth impaired driving deaths

OBJECTIVE: To explore associations of state retail alcohol monopolies with underage drinking and alcohol-impaired driving deaths. DATA: Surveys on youth who drank alcohol and binge-drank recently and their beverage choices; census of motor vehicle fatalities by driver blood alcohol level. METHODS: Regressions estimated associations of monopolies with under-21 drinking, binge drinking, alcohol-impaired driving deaths, and odds a driver under 21 who died was alcohol-positive. RESULTS: About 93.8% of those ages 12-20 who consumed alcohol in the past month drank some wine or spirits. In states with a retail monopoly over spirits or wine and spirits, an average of 14.5% fewer high school students reported drinking alcohol in the past 30 days and 16.7% fewer reported binge drinking in the past 30 days than high school students in non-monopoly states. Monopolies over both wine and spirits were associated with larger consumption reductions than monopolies over spirits only. Lower consumption rates in monopoly states, in turn, were associated with a 9.3% lower alcohol-impaired driving death rate under age 21 in monopoly states versus non-monopoly states. Alcohol monopolies may prevent 45 impaired driving deaths annually. CONCLUSIONS: Continuing existing retail alcohol monopolies should help control underage drinking and associated harms.     

The alpha-to-beta conformational transition of Alzheimer's Abeta-(1-42) peptide in aqueous media is reversible: a step by step conformational analysis suggests the location of beta conformation seeding

Current views of the role of beta-amyloid (Abeta) peptide fibrils range from regarding them as the cause of Alzheimer's pathology to having a protective function. In the last few years, it has also been suggested that soluble oligomers might be the most important toxic species. In all cases, the study of the conformational properties of Abeta peptides in soluble form constitutes a basic approach to the design of molecules with "antiamyloid" activity. We have experimentally investigated the conformational path that can lead the Abeta-(1-42) peptide from the native state, which is represented by an alpha helix embedded in the membrane, to the final state in the amyloid fibrils, which is characterized by beta-sheet structures. The conformational steps were monitored by using CD and NMR spectroscopy in media of varying polarities. This was achieved by changing the composition of water and hexafluoroisopropanol (HFIP). In the presence of HFIP, beta conformations can be observed in solutions that have very high water content (up to 99 % water; v/v). These can be turned back to alpha helices simply by adding the appropriate amount of HFIP. The transition of Abeta-(1-42) from alpha to beta conformations occurs when the amount of water is higher than 80 % (v/v). The NMR structure solved in HFIP/H2O with high water content showed that, on going from very apolar to polar environments, the long N-terminal helix is essentially retained, whereas the shorter C-terminal helix is lost. The complete conformational path was investigated in detail with the aid of molecular-dynamics simulations in explicit solvent, which led to the localization of residues that might seed beta conformations. The structures obtained might help to find regions that are more affected by environmental conditions in vivo. This could in turn aid the design of molecules able to inhibit fibril deposition or revert oligomerization processes.     

Influence of strontium for calcium substitution in bioactive glasses on degradation,ion release and apatite formation

Bioactive glasses are able to bond to bone through the formation of hydroxy-carbonate apatite in body fluids while strontium (Sr)-releasing bioactive glasses are of interest for patients suffering from osteoporosis, as Sr was shown to increase bone formation both in vitro and in vivo. A melt-derived glass series (SiO₂–P₂O₅–CaO–Na₂O) with 0–100% of calcium (Ca) replaced by Sr on a molar base was prepared. pH change, ion release and apatite formation during immersion of glass powder in simulated body fluid and Tris buffer at 37°C over up to 8 h were investigated and showed that substituting Sr for Ca increased glass dissolution and ion release, an effect owing to an expansion of the glass network caused by the larger ionic radius of Sr ions compared with Ca. Sr release increased linearly with Sr substitution, and apatite formation was enhanced significantly in the fully Sr-substituted glass, which allowed for enhanced osteoblast attachment as well as proliferation and control of osteoblast and osteoclast activity as shown previously. Studying the composition–structure–property relationship in bioactive glasses enables us to successfully design next-generation biomaterials that combine the bone regenerative properties of bioactive glasses with the release of therapeutically active Sr ions.     

Extension of the Stokes equation for layered constructions to fluorescent turbid media

Expressions relating the bispectral reflectance of a stack of n fluorescing layers to each individual layer's reflectance and transmittance are derived. This theoretical framework is used together with recently proposed extensions of the Kubelka-Munk model to study the fluorescence from layered turbid media. For one layer over a reflecting background, the model is shown to give the same results as a previous model. The extension to n layers with different optical properties allows simulating the bispectral reflectance from a pad of layered turbid media. The applicability of the model is exemplified with an optimization of fluorophore distribution in layered turbid media.     

Methane decomposition over Co thin layer supported catalysts to produce hydrogen for fuel cell

Co/Al₂O₃/Silica Cloth Thin Layer Catalysts (CoAS) for Catalytic Decomposition of Natural Gas (CDNG) were investigated using a new Multilayer Catalytic Reactor (MCR). The influence of Co loading and reaction temperature was evaluated. Irrespective of Co loading, initial CH₄ conversion rises with T_R, while for lifetime and carbon capacity (C/Ni, number of CH₄ molecules decomposed for Ni atom until complete deactivation) it is not possible to find a direct relationship with other operating parameters or catalyst characteristics. However, Co loading significantly affects the catalytic activity: Co loading as high as 20 wt.% ensures both long lifetime and high H₂ productivity. On the contrary of what occurs using Ni-based catalysts and irrespective of reaction temperature investigated, filamentous coke forms with a “base” reaction mechanism and Co catalyst can be regenerated in oxygen without any problem, thus allowing to realize a dual-step process for the production of “CO_x-free” hydrogen stream.     

Effect of austenitising conditions on the impact properties of an alloyed austempered ductile iron of initially pearlitic matrix structure

This study sets out to investigate the effect of austenitising conditions on the microstructure and impact properties of an austempered ductile iron containing Copper and Nickel and having an initially fully pearlitic structure. Un-notched Izod impact test specimens were solution treated in the range 850–1000 °C for durations between 15 and 360 min. and then austempered at 360 °C for 180 min.

It was shown that increasing the austenitising temperature increases the amount of carbon taken in solution by the original austenite. This reduces the driving force controlling the transformation of the austenite to the ausferrite product, ferrite and austenite. As a result, the retained austenite volume in the final microstructure increases but simultaneously its stability falls. This places an upper limit on the austenitising temperature and the amount of retained austenite permissible. On the other hand, for optimum properties, the austenitising temperature and time must be high and long enough respectively to ensure complete austenitisation.

It was also shown that generally, in irons with an initially pearlitic structure, the impact properties increase steadily to a maximum value as the austenitising time increases to about 180 min. and remain constant as the soaking period extends further. Optimum properties are obtained following austenitising between 850 and 900 °C for durations of 120 to 180 min. and correspond to heat treatment cycles which saturate the initial austenite with carbon.     

The epidemiology and cost of falls requiring hospitalisation in children in Western Australia: a study using linked administrative data

OBJECTIVE: The aim of this study was to examine the epidemiology and health system cost of children's falls resulting in hospitalisation in 2003 in Western Australia. METHODS: The Injury Cost Database was used to identify children who were admitted to hospital with a falls related injury. Adjusted incidence rate ratios (IRR) of hospitalisation were modelled using Poisson regression. In-patient hospital costs were assigned using the published DRG costs for Western Australia. These costs were then extrapolated to health system costs based on previously published relative proportions. RESULTS: When adjusted for other covariates in the model males had a 53% higher incidence of falls requiring hospitalisation compared with females. Aboriginal children had a 36% higher incidence compared with their non-Aboriginal counterparts, and the incidence of falls reduced with increasing age. The total cost of in-patient hospitalisation associated with children's falls in Western Australia was A$4,554,000 with an average cost of A$1876 per case. In children aged 0-4 years and 10-14 years the highest cost resulted from falls on the flat (slips and trips). However, in children aged 5-9 years injuries resulting from falls from playground equipment resulted in both the highest cost group (A$539,000) and the highest cost per case (A$1917). The total cost to the health system of children's falls in Western Australia in 2003 were estimated to be A$21.5 million, with the total cost to the community estimated at A$108.5 million. CONCLUSION: Children's falls impose a considerable burden and cost to both the health care system and the community. This study has provided information on where the burden of risk and the majority of costs lie, namely males, Aboriginal children and for children aged 5-9 years, unlike their younger and older peers, playground equipment.