Comparison of Structure‐ and Ligand‐Based Virtual Screening Protocols Considering Hit List Complementarity and Enrichment Factors

Structure‐ and ligand‐based virtual‐screening methods (docking, 2D‐ and 3D‐similarity searching) were analysed for their effectiveness in virtual screening against four different targets: angiotensin‐converting enzyme (ACE), cyclooxygenase 2 (COX‐2), thrombin and human immunodeficiency virus 1 (HIV‐1) protease. The relative performance of the tools was compared by examining their ability to recognise known active compounds from a set of actives and nonactives. Furthermore, we investigated whether the application of different virtual‐screening methods in parallel provides complementary or redundant hit lists. Docking was performed with GOLD, Glide, FlexX and Surflex. The obtained docking poses were rescored by using nine different scoring functions in addition to the scoring functions implemented as objective functions in the docking algorithms. Ligand‐based virtual screening was done with ROCS (3D‐similarity searching), Feature Trees and Scitegic Functional Fingerprints (2D‐similarity searching). The results show that structure‐ and ligand‐based virtual‐screening methods provide comparable enrichments in detecting active compounds. Interestingly, the hit lists that are obtained from different virtual‐screening methods are generally highly complementary. These results suggest that a parallel application of different structure‐ and ligand‐based virtual‐screening methods increases the chance of identifying more (and more diverse) active compounds from a virtual‐screening campaign.     

Hot corrosion studies of a salt-coated Ni-based superalloy under flowing wet air and sulfur vapor ambient

Corrosion of a salt-coated Ni-superalloy has been studied at 900°C under a wet air and sulfur vapor ambient. The corrosion thickness, after an incubation of ~60 hr, linearly increases with the corrosion time t and the onset of surface spallation occurred at t ≈ 60 hr. The corroded layer consists of a corrosion front dominated by Cr₃S₄ scales and linear precipitate structures, an inner corrosion layer dominated by Ni₃S₂ and NiO, and an outer corrosion layer dominated by Al₂O₃ networks surrounding the Ni₃S₂ and/or NiO scale structures. The corrosion mechanism is discussed based on the coexistence of H₂O, sulfur, and oxygen.     

Treatment with the Probiotic Product Aviguard® Alleviates Inflammatory Responses during Campylobacter jejuni-Induced Acute Enterocolitis in Mice

Prevalences of Campylobacter (C.) jejuni infections are progressively rising globally. Given that probiotic feed additives, such as the commercial product Aviguard^®, have been shown to be effective in reducing enteropathogens, such as Salmonella, in vertebrates, including livestock, we assessed potential anti-pathogenic and immune-modulatory properties of Aviguard^® during acute C. jejuni-induced murine enterocolitis. Therefore, microbiota-depleted IL-10^−/− mice were infected with C. jejuni strain 81-176 by gavage and orally treated with Aviguard^® or placebo from day 2 to 4 post-infection. The applied probiotic bacteria could be rescued from the intestinal tract of treated mice, but with lower obligate anaerobic bacterial counts in C. jejuni-infected as compared to non-infected mice. Whereas comparable gastrointestinal pathogen loads could be detected in both groups until day 6 post-infection, Aviguard^® treatment resulted in improved clinical outcome and attenuated apoptotic cell responses in infected large intestines during acute campylobacteriosis. Furthermore, less distinct pro-inflammatory immune responses could be observed not only in the intestinal tract, but also in extra-intestinal compartments on day 6 post-infection. In conclusion, we show here for the first time that Aviguard^® exerts potent disease-alleviating effects in acute C. jejuni-induced murine enterocolitis and might be a promising probiotic treatment option for severe campylobacteriosis in humans.     

Expanding the analytical potential of channel locational probability maps using cellular statistics

The planimetric shifts in channel location of large alluvial rivers are a critical component in the creation of diverse structures and functions in riverine habitats. Engineered management schemes must also compensate for this type of channel change to protect resources and maintain navigation channels. The stability of the Lower Mississippi River channel was assessed through an analysis of historical records of channel position produced and archived by the United States Army Corps of Engineers. Channel location was recorded for the years 1765, 1820, 1881, 1915, 1930, 1937, 1960 and 1970. Channel stability was measured by two introduced metrics on a cell‐by‐cell basis: (1) the standard deviation of Euclidean distance to a channel cell for the entire period of record, and (2) the rate of Euclidean distance change between years in the period of record. At a coarse spatial scale, channel instability increased in the downstream direction. The variability of channel stability also increased in the downstream direction. Analysis of this variability identified alternating areas of high and low stability occurring with greater frequency as distance downstream increased. These findings are validated by past studies of channel stability along the Lower Mississippi River. As a result, the proposed metrics provide a consistent, quantitative, efficient and cost‐effective means of identifying areas of channel instability at several spatial scales. Copyright © 2006 John Wiley & Sons, Ltd.     

Implications to stormwater management as a result of lot scale rainwater tank systems: a case study in Western Sydney, Australia

Rainwater tanks are increasingly adopted in Australia to reduce potable water demand and are perceived to reduce the volume of stormwater discharge from developments. This paper investigates the water balance of rainwater tanks, in particular the possible impacts these tanks could have in controlling the stormwater discharge volume. The study collected water quantity data from two sites in the Hawkesbury City Council area, New South Wales, Australia and utilised the collected data in a simple water balance model to assess the effectiveness of rainwater tanks in reducing the stormwater discharge volume. The results indicate that a significant reduction in discharge volume from a lot scale development can be achieved if the rainwater tank is connected to multiple end-uses, but is minimal when using irrigation alone. In addition, the commonly used volumetric runoff coefficient of 0.9 was found to over-estimate the runoff from the roof areas and to thereby under-estimate the available volume within the rainwater tanks for retention or detention. Also, sole reliance on the water in the rainwater tanks can make the users aware of their water use pattern and water availability, resulting in significant reductions in water use as the supply dwindles, through self-imposed water restrictions.     

Oxalylhydrazinium Nitrate and Dinitrate—Efficiency Meets Performance

Oxalylhydrazinium nitrate (OHN) and dinitrate (OHDN) were synthesized by protonation of oxalyldihydrazide with nitric acid. The synthesis is extremely cost effective (～$40/kg at the lab scale) and can be carried out in large scales and very good yields. OHN and OHDN were intensively characterized by low-temperature X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and vibrational spectroscopy. These new organic nitrate salts could be used as powerful ingredients in energetic formulations due to their low sensitivities (measured by Bundesanstalt für Materialforschung und Pröfung methods). Their thermal stability was investigated by differential scanning calorimetry (DSC) measurements. Further thermal studies of OHN showed compatibility with TNT (2,4,6-trinitrotoluene), DNAN (2,4-dinitroanisole), and RDX (1,3,5-trinitro-1,3,5-triazinane). The theoretical detonation and propulsion parameters of OHN and OHDN were calculated with the EXPLO5.5 code and compared to well-known insensitive explosives. The aquatic toxicity of OHN was determined by the luminescent bacteria inhibition test, yielding a much lower toxicity than RDX.     

LIQUID PHASE CO-OXIDATION OF THIOPHENOL AND STYRENE BY OXYGEN AND t-BUTYL HYDROPEROXIDE

ABSTRACT

Instability problems in both shale and petroleum derived middle distillate jet fuels have been correlated with the presence of peroxidic species. Although a good body of knowledge exists concerning the formation of peroxides in the liquid phase, relatively little is known about the reaction/ decomposition pathways available when other functional groups are present, since sulfur is the most abundant heteroatam present in jet fuels, the reaction of t-butyl hydroperoxide (tBKP) and/or oxygen with thiophenol in the presence of the active olefin, styrene, was examined in deaerated benzene at 120°C. The complex product mixture was analyzed by combined capillary column GC/MS. Major products included acetone, t-butanol and isdbutylene from the tBHP. Thiophenol and styrene combined to form addition products. Phenyl disulfide was observed from the thiophenol. The results indicated that although the product slate was complex, it was possible to explain the product mix in terms of a few competing reactions.     

FUEL INSTABILITY STUDIES: LIQUID PHASE OXIDATION OF TETRAHYDROTHIOPHENE BY TERT-BUTYL HYDROPEROXIDE

ABSTRACT

The reactions that lead to fuel instability are the subject of conflicting reports in the literature. Confusion results from the difficulty in relating differences in fuel composition, temperature, surface effects and dissolved oxygen content that comprise the multitude of reported studies. Model studies offer a means by which the mechanism of an individual reaction can be related to a simple system and then extended to the more complex fuel media. This paper reports a model oxidation study of a cyclic sulfide, tetrahydrothiophene, with an active oxygen species, t-butyl hydroperoxide under mild reaction conditions, 120°C, in a tetradecane model fuel. The major oxidation product was tetrahydrothiophene sulfoxide from the sulfide and t-butanol from the hydroperoxide. The complete suite of products is reported.     

Laminar flow of non-linear viscoelastic fluids in straight tubes of arbitrary contour

The fully developed steady velocity field in pressure gradient driven laminar flow of non-linear viscoelastic fluids with instantaneous elasticity constitutively represented by a class of single mode, non-affine quasilinear constitutive equations is investigated in straight pipes of arbitrary contour ?D. A continuous one-to-one mapping is used to obtain arbitrary tube contours from a base tube contour ?D₀. The analytical method presented is capable of predicting the velocity field in tubes with arbitrary cross-section. The base flow is the Newtonian field and is obtained at O(1). Field variables are expanded in asymptotic series in terms of the Weissenberg number Wi. The analysis does not place any restrictions on the smallness of the driving pressure gradients which can be large and applies to dilute and weakly elastic non-linear viscoelastic fluids. The velocity field is investigated up to and including the third order in Wi. The Newtonian field in general arbitrary contours is obtained and longitudinal velocity field components due to shear-thinning and to non-linear viscoelastic effects are identified. Third order analysis shows a further contribution to the longitudinal field driven by first normal stress differences. Secondary flows driven by unbalanced second normal stresses in the cross-section manifest themselves as well at this order. Longitudinal equal velocity contours, the secondary flow field structure, the first and the second normal stress differences as well as wall shear stress variations are discussed for several non-circular contours some for the first time.