Divergent Synthesis of Novel Cylindrocyclophanes that Inhibit Methicillin-Resistant Staphylococcus aureus (MRSA)

The cylindrocyclophanes are a family of macrocyclic natural products reported to exhibit antibacterial activity. Little is known about the structural basis of this activity due to the challenges associated with their synthesis or isolation. We hypothesised that structural modification of the cylindrocyclophane scaffold could streamline their synthesis without significant loss of activity. Herein, we report a divergent synthesis of the cylindrocyclophane core enabling access to symmetrical macrocycles by means of a catalytic, domino cross-metathesis-ring-closing metathesis cascade, followed by late-stage diversification. Phenotypic screening identified several novel inhibitors of methicillin-resistant Staphylococcus aureus. The most potent inhibitor has a unique tetrabrominated [7,7]paracyclophane core with no known counterpart in nature. Together these illustrate the potential of divergent synthesis using catalysis and unbiased screening methods in modern antibacterial discovery.     

Static fatigue of Hi-Nicalon™-S fiber at elevated temperature in air,steam, and silicic acid-saturated steam

A facility for testing SiC fiber tows in static fatigue and creep at elevated temperatures in air and steam was developed. Static fatigue of Hi-Nicalon™-S fibers was investigated at 800°C-1100°C at applied stresses between 115 and 1250 MPa in air, in Si(OH)₄(g)-saturated steam, and in unsaturated steam. Fibers tested in Si(OH)₄(g)-saturated steam and in air had silica scales throughout the test sections, but those tested in unsaturated steam did not develop scales near the steam injection point. Fiber lifetimes in static fatigue were shortest in unsaturated steam, intermediate in Si(OH)₄(g)-saturated steam, and longest in air. Failure strains did not exceed 0.3%. Steady-state strain rates and static fatigue lifetimes are modelled empirically by the Monkman-Grant relationship. Failure mechanisms are discussed.     

Molecular subtypes of Campylobacter spp., Salmonella enterica, and Escherichia coli O157:H7 isolated from faecal and surface water samples in the Oldman River watershed, Alberta, Canada

Campylobacter spp., Salmonella enterica, and Escherichia coli O157:H7 isolated from 898 faecal, 43 sewage, and 342 surface water samples from the Oldman River were characterized using bacterial subtyping methods in order to investigate potential sources of contamination of the watershed. Among these pathogens, Campylobacter spp. were the most frequently isolated from faecal, sewage, and surface water samples (266/895, 11/43, and 91/342, respectively), followed by Salmonella (67/898, 8/43, and 29/342, respectively), and E. coli O157:H7 (16/898, 2/43, and 8/342, respectively). Salmonella Rubislaw was the most common serovar isolated from water. This serovar was also isolated from two wild bird species. Most other serovars isolated from water were either not isolated from animals or were isolated from multiple species. E. coli O157:H7 was predominantly isolated from cattle. The most common phage-types of this pathogen from cattle were also the most common among water isolates, and there were exact pulsed field gel electrophoresis and comparative genomic fingerprint matches between cattle, sewage, and water isolates. Campylobacters were commonly isolated from surface waters and faeces from most animal species. Restriction fragment length polymorphism of the Campylobacter flaA gene identified several location and host species-specific (cattle, goose, pig) fingerprints. Molecular subtyping of these bacterial pathogens shows considerable promise as a tool for determining the sources of faecal pollution of water.     

Chlorinated organics from chlorine used in water treatment

The contribution from impurities in chlorine to levels of chlorinated organics found in potable water after chlorination was investigated. Techniques for sampling of chlorine and gas chromatography (GC) determination of chlorinated organics in chlorine are described. The detection limits were better than 1 ppm for each of chloromethane, dichloromethane, chloroform, carbon tetrachloride, trichloroethylene, tetrachloroethylene, hexachloroethane, hexachloropropane and hexachlorobenzene in chlorine. With the exception of chloroform which occasionally accounted for nearly 1 μg l⁻¹ in water, the levels of the nine compounds in chlorine accounted for less than 0.1 μg l⁻¹ of each compound in chlorinated water from 10 Canadian treatment plants. The occurrence of these nine and 28 additional chlorinated organics previously detected in water supplies was determined by aid of liquid-liquid extraction of water samples. Seven compounds, including chloroform, carbon tetrachloride, trichloroethylene and tetrachloroethylene were detected, usually at levels ranging from 0.1 to 1 μg l⁻¹ in chlorinated water from the treatment plant.     

Quantitative Physiological Assessment of Stress Via Altered Immune Functioning Following Interaction With Differing Automotive Interface Technologies

Technology can enhance or diminish a user's psycho-physiological stress level; the ability to quantify these responses can help evaluate and refine design. The capability of drivers to accomplish basic tasks utilizing differing sensory modalities while maintaining lane discipline within a computer-simulated environment was assessed. Fifteen healthy subjects provided capillary blood samples before and after using three human–machine interface designs—touch-screen, voice control, and multimodal. Using a chemiluminescent technique termed Leukocyte Coping Capacity, the ability of leukocytes to produce reactive oxygen species in vitro was assessed. Significant poststressor changes in leukocyte activity of varying magnitude were observed following the use of all interfaces; with the multimodal interface provoking the most pronounced response and voice control the least. Although still requiring further research, the results support the proposition for using immune responsiveness as a means for quantifying psychological stress during assessment of ergonomic design and psycho-physiological and social interaction.     

Hydrogen-induced intergranular failure in nickel revisited

Using a combination of high-resolution scanning and transmission electron microscopy, the basic mechanisms of hydrogen-induced intergranular fracture in nickel have been revisited. Focused-ion beam machining was employed to extract samples from the fracture surface to enable the examination of the microstructure immediately beneath it. Evidence for slip on multiple slip systems was evident on the fracture surface; immediately beneath it, an extensive dislocation substructure exists. These observations raise interesting questions about the role of plasticity in establishing the conditions for hydrogen-induced crack initiation and propagation along a grain boundary. The mechanisms of hydrogen embrittlement are re-examined in light of these new results.     

Microstructure and Hydrogen-Induced Failure Mechanisms in Fe and Ni Alloy Weldments

The microstructure and fracture morphology of AISI 8630-IN625 and ASTM A182-F22-IN625 dissimilar metal weld interfaces were compared and contrasted as a function of postweld heat treatment (PWHT) duration. For both systems, the microstructure along the weld interface consisted of a coarse grain heat-affected zone in the Fe-base metal followed by discontinuous martensitic partially mixed zones and a continuous partially mixed zone on the Ni side of the fusion line. Within the partially mixed zone on the Ni side, there exists a 200-nm-wide transition zone within a 20-??m-wide planar solidification region followed by a cellular dendritic region with Nb-Mo?Crich carbides decorating the dendrite boundaries. Although there were differences in the volume of the partially mixed zones, the major difference in the metal weld interfaces was the presence of M₇C₃ precipitates in the planar solidification region, which had formed in AISI 8630-IN625 but not in ASTM A182-F22-IN625. These precipitates make the weldment more susceptible to hydrogen embrittlement and provide a low energy fracture path between the discontinuous partially mixed zones.