Genetic effects of 1,3-butadiene and associated risk for heritable damage

A summary of the results of the studies conducted in the EU Project "Multi-endpoint analysis of genetic damage induced by 1,3-butadiene and its major metabolites in somatic and germ cells of mice, rats and man" is presented. Results of the project are summarized on the detection of DNA and hemoglobin adducts, on the cytotoxic and clastogenic effects in somatic and germinal cells of mice and rats, on the induction of somatic mutations at the hprt locus of experimental rodents and occupationally exposed workers, on the induction of dominant lethal mutations in mice and rats, and on heritable translocations induced in mice, after exposure to butadiene (BD) or its major metabolites, butadiene monoepoxide (BMO), diepoxybutane (DEB) and butadiene diolepoxide (BDE). The primary goal of this project was to collect experimental data on the genetic effects of BD in order to estimate the germ cell genetic risk to humans of exposure to BD. To achieve this, the butadiene exposure are based on data for heritable translocations and bone marrow micronuclei induced in mice and chromosome aberrations observed in lymphocytes of exposed workers. A doubling dose for heritable translocations in human germ cells of 4900 ppm/h is estimated, which, assuming cumulative BD exposure over the sensitive period of spermatogenesis, corresponds to 5-6 weeks of continuous exposure at the workplace to 20-25 ppm. Alternatively, the rate of heritable translocation induction per ppm/h of BD exposure is estimated to be approximately 0.8 per million live born, compared to a spontaneous incidence of balanced translocations in humans of approximately 800 per million live born. These estimates have large confidence intervals and are only intended to indicate orders of magnitude of human genetic risk. These risk estimates are based on data from germ cells of BD-exposed male mice. The demonstration that clastogenic damage was induced by DEB in preovulatory oocytes at doses which were not ovotoxic implies that additional studies on the response of mammalian female germ cells to BD and its metabolites are needed. The basic assumption of the above genetic risk estimates is that experimental mouse data obtained after BD exposure can be extrapolated to humans. Several points exist in the present report and in the literature which contradict this assumption: (1) the level of BMO-hemoglobin adducts was significantly elevated in BD-exposed workers; however, it was considerably lower than would have been predicted from comparable rat and mouse exposures; (2) the concentrations of the metabolites DEB and BMO were significantly higher in mouse than in rat blood after BD exposure. Thus, while metabolism of BD is qualitatively similar in the two species, it is quantitatively different; (3) no increase of HPRT mutations was shown in 19 workers exposed on average to 1.8 ppm of BD, while in a different population of workers from a US plant exposed on average to 3.5 ppm of BD, a significant increase of HPRT variants was detected; and (4) data from cancer bioassays and cancer epidemiology suggest that rat is a more appropriate model than mouse for human cancer risk from BD exposure. However, the dominant lethal study in rats gave a negative result. At present, we do not know which BD metabolite(s) may be responsible for the genetic effects even though the bifunctional alkylating agent DEB is the most likely candidate for the induction of clastogenic events. Unfortunately, methods to measure DEB adducts in hemoglobin or DNA are only presently being developed. Despite these several uncertainties the use of the mouse genetic data is regarded as a justifiable and conservative approach to human genetic risk estimation given the considerable heterogeneity observed in the biotransformation of BD in humans.     

Amplification of high-order rainbows of a cylinder with an elliptical cross section

The intensity of high-order rainbows for normally incident light and certain rotation angles of a cylinder with an elliptical cross section is greatly amplified with respect to the intensity for a circular cross-sectional cylinder. The amplification is due to a number of the internal reflections occurring past the critical angle for total internal reflection, and the effect is especially strong for odd-order rainbows, beginning with the third order. Experimentally, the fourth- and the fifth-order rainbows of a nearly elliptical cross-sectional glass rod were observed and analyzed.     

High temperature faraday balance for in situ measurement of magnetization in transition metal oxides

We report the design of a Faraday balance that can be used to measure the magnetization of transition metal oxides at high temperatures and under controlled atmosphere. The instrument is sufficiently sensitive and stable to quantify the magnetic force on diamagnetic and paramagnetic samples at temperatures up to 1000 degrees C and in oxygen partial pressures as low as 100 ppm. We demonstrate the performance of the instrument by presenting preliminary magnetic measurements of lanthanum strontium cobalt oxide (La1-xSr(x)CoO3-delta) and aluminum oxide (Al2O3).     

Evaluation of time-dependent and quantitative properties of contraction from left ventricular pressure

Several mechanical indices predicted from a model of cardiac muscle contraction are tested. In the in-vivo canine heart, dp/dtmax and t-dp/dt, the time interval from onset of contraction to dp/dtmax, were measured. The product of these parameters Ap = t-dp/dtmax was calculated. t-dp/dt was shortened when heart rate was elevated and remained constant when ventricular end diastolic volume was changed. Ap increased with augmentation of ventricular end diastolic volume. To achieve constant muscle length when heart rate is changed, analogous tension measurements (assigned as dT/dtmax, t-dT/dt and AT) of prestretched Walton Brodie strain-gauge arch had been taken instead of pressure measurements. In the experiments in which Tmax, maximal isometric tension, was not changed for various heart rates, AT was also unchanged. These results are consistent with the predictions that t-dp/dt and Ap can be used as two independent mechanical indices: 1) t-dp/dt for the evaluation of the "time-dependent properties" of contraction and 2) Ap, for the evaluation of the "quantitative properties" of contraction. The advantages of applying these two mechanical indices for use in the intact ejecting heart, instead of the well-established parameters Vmax and Po are emphasized.     

Holography: a behavior‐based profiler for malware analysis

Behavior‐based detection and signature‐based detection are two popular approaches to malware (malicious software) analysis. The security industry, such as the sector selling antivirus tools, has been using signature and heuristic‐based technologies for years. However, this approach has been proven to be inefficient in identifying unknown malware strains. On the other hand, the behavior‐based malware detection approach has a greater potential in identifying previously unknown instances of malicious software. The accuracy of this approach relies on techniques to profile and recognize accurate behavior models. Unfortunately, with the increasing complexity of malicious software and limitations of existing automatic tools, the current behavior‐based approach cannot discover many newer forms of malware either. In this paper, we implement ‘holography platform’, a behavior‐based profiler on top of a virtual machine emulator that intercepts the system processes and analyzes the CPU instructions, CPU registers, and memory. The captured information is stored in a relational database, and data mining techniques are used to extract information. We demonstrate the breadth of the ‘holography platform’ by conducting two experiments: a packed binary behavior analysis and a malvertising (malicious advertising) incident tracing. Both tasks are known to be very difficult to do efficiently using existing methods and tools. We demonstrate how the precise behavior information can be easily obtained using the ‘holography platform’ tool. With these two experiments, we show that the ‘holography platform’ can provide security researchers and automatic malware detection systems with an efficient malicious software behavior analysis solution. Copyright © 2011 John Wiley & Sons, Ltd.     

Fast Minor Testing in Planar Graphs

Minor Containment is a fundamental problem in Algorithmic Graph Theory used as a subroutine in numerous graph algorithms. A model of a graph H in a graph G is a set of disjoint connected subgraphs of G indexed by the vertices of H, such that if {u,v} is an edge of H, then there is an edge of G between components C _u and C _v . A graph H is a minor of G if G contains a model of H as a subgraph. We give an algorithm that, given a planar n-vertex graph G and an h-vertex graph H, either finds in time $\mathcal{O}(2^{\mathcal{O}(h)} \cdot n +n^{2}\cdot\log n)$ a model of H in G, or correctly concludes that G does not contain H as a minor. Our algorithm is the first single-exponential algorithm for this problem and improves all previous minor testing algorithms in planar graphs. Our technique is based on a novel approach called partially embedded dynamic programming.     

Filtered vacuum arc deposition of transparent conducting Al-doped ZnO films

Transparent conducting ZnO:Al and ZnO films of 380-800 nm thickness were deposited on glass substrates by filtered vacuum arc deposition (FVAD), using a cylindrical Zn cathode doped with 5-6 at.% Al or a pure Zn cathode in oxygen background gas with pressure P = 0.4-0.93 Pa. The crystalline structure, composition and electrical and optical properties of the films were studied as functions of P. The films were stored under ambient air conditions and the variation of their resistance as function of storage time was monitored over a period of several months.The Al concentration in the film was found to be 0.006-0.008 at.%, i.e., a few orders of magnitude lower than that in the cathode material. However, this low Al content influenced the film resistivity, ρ, and its stability. The resistivity of as-deposited ZnO:Al films, ρ = (6-8) × 10^− 3 Ω cm, was independent of P and lower by a factor of 2 in comparison to that of the ZnO films deposited by the same FVAD system. The ρ of ZnO films 60 days after deposition increased by a factor of ∼ 7 with respect to as-deposited films. The ZnO:Al films deposited with P = 0.47-0.6 Pa were more stable, their ρ first slowly increased during the storage time (1.1-1.4 times with respect to as-deposited films), and then stabilized after 30-45 days.     

The emergence of distributed component platforms

Several vendors and consortia have independently developed standards that define the basic mechanics for building and interconnecting software components. Sun's JavaBeans has emerged as the leading rival to Microsoft's DCOM, supplanting the OpenDoc standard from the now defunct Component Integration Laboratories. Component software is moving from its original focus on desktop-bound compound documents to enterprise applications that include distributed server components. The backers of competing standards are racing to capture market leadership by delivering the tangible benefits of component standards via distributed component platforms-integrated development and runtime environments that isolate much of the conceptual and technical complexity involved in building component-based applications. With DCPs, businesses can assign their few highly skilled programmers to component construction and use less sophisticated developers to carry out the simpler assembly tasks. By making component standards available to the broadest possible spectrum of developers, DCPs essentially drive those standards to market. This article reviews the state of component software as embodied in DCPs. The two DCP market leaders are Microsoft's DCOM (or ActiveX/DCOM) and Sun's JavaBeans. However, Internet and OMG component standards are emerging that will likely impact both the content and status of these two DCPs. The article also discusses component frameworks, which extend DCPs to provide more complete application development solutions