Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors

Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world′s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin‐inspired derivatives, namely 3,5‐isoxazoles, furoxans, and furazans. Several of these compounds maintain low‐micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.     

On-line determination of supersaturation of a kcl-nacl aqueous solution based on density measurement

A method is developed for the calculation of the saturation temperature of a KCI-NaCI aqueous solution, based on the measurement of the density and temperature of a sample solution, and prior knowledge of the NaCl concentration. Experimental density and solubility data for solutions saturated with KCI in the temperature range of 299 to 321 K with concentrations of NaCl greater than 0.200 kg/kg H₂O were used to develop the empirical correlation allowing the calculation of the solution saturation level. The method is applicable in the on-line determination of the level of supersaturation in a KCI crystallizer in which the NaCl concentration is known. Knowledge of the prevailing supersaturation is necessary for the control of crystal purity and crystal size distribution in industrial potash crystallizers.     

Factors affecting the sensitivity of e-beam resists

In order to determine the effects of chemical structure on electron beam resist sensitivities, a series of polymers with different reactive components and additives has been investigated. The results, based on a larger number of exposures varying over five orders of magnitude, point out several interesting facts. The data indicate that the sensitivity of negative resists is not a linear function of molecular weight as previously supposed. Also, the negative electron resists tend to be more sensitive and cover a broader range of sensitivities than positive resists. The results further show that olefin and epoxy groups greatly enhance the crosslinking rate of these exposed polymers. However, additives, which are good energy transferring type sensitizers, have little effect on resist sensitivity. This last result is not surprising considering the nonselectivity of the exciting electrons.     

Photothermal nanoblade for large cargo delivery into mammalian cells

It is difficult to achieve controlled cutting of elastic, mechanically fragile, and rapidly resealing mammalian cell membranes. Here, we report a photothermal nanoblade that utilizes a metallic nanostructure to harvest short laser pulse energy and convert it into a highly localized explosive vapor bubble, which rapidly punctures a lightly contacting cell membrane via high-speed fluidic flows and induced transient shear stress. The cavitation bubble pattern is controlled by the metallic structure configuration and laser pulse duration and energy. Integration of the metallic nanostructure with a micropipet, the nanoblade generates a micrometer-sized membrane access port for delivering highly concentrated cargo (5 × 10(8) live bacteria/mL) with high efficiency (46%) and cell viability (>90%) into mammalian cells. Additional biologic and inanimate cargo over 3-orders of magnitude in size including DNA, RNA, 200 nm polystyrene beads, to 2 μm bacteria have also been delivered into multiple mammalian cell types. Overall, the photothermal nanoblade is a new approach for delivering difficult cargo into mammalian cells.     

A comparison of the hazard perception ability of accident-involved and accident-free motorcycle riders

Hazard perception is the ability to read the road and is closely related to involvement in traffic accidents. It consists of both cognitive and behavioral components. Within the cognitive component, visual attention is an important function of driving whereas driving behavior, which represents the behavioral component, can affect the hazard perception of the driver. Motorcycle riders are the most vulnerable types of road user. The primary purpose of this study was to deepen our understanding of the correlation of different subtypes of visual attention and driving violation behaviors and their effect on hazard perception between accident-free and accident-involved motorcycle riders. Sixty-three accident-free and 46 accident-involved motorcycle riders undertook four neuropsychological tests of attention (Digit Vigilance Test, Color Trails Test-1, Color Trails Test-2, and Symbol Digit Modalities Test), filled out the Chinese Motorcycle Rider Driving Violation (CMRDV) Questionnaire, and viewed a road-user-based hazard situation with an eye-tracking system to record the response latencies to potentially dangerous traffic situations. The results showed that both the divided and selective attention of accident-involved motorcycle riders were significantly inferior to those of accident-free motorcycle riders, and that accident-involved riders exhibited significantly higher driving violation behaviors and took longer to identify hazardous situations compared to their accident-free counterparts. However, the results of the regression analysis showed that aggressive driving violation CMRDV score significantly predicted hazard perception and accident involvement of motorcycle riders. Given that all participants were mature and experienced motorcycle riders, the most plausible explanation for the differences between them is their driving style (influenced by an undesirable driving attitude), rather than skill deficits per se. The present study points to the importance of conceptualizing the influence of different driving behaviors so as to enrich our understanding of the role of human factors in road accidents and consequently develop effective countermeasures to prevent traffic accidents involving motorcycles.     

Rates of molecular vaporization of organic plasticizers

The kinetics of the molecular vaporization process of 21 plasticizers were investigated in detail. By both isothermal and nonisothermal kinetic methods, it was evident that 11 were quite pure single compounds, while 10 were clearly mixtures of compounds. For the single component species internal energies for vaporization and rates of volatilization are listed. The internal energies of vaporization are about one-half or less of values one can estimate from the additive factor method of Small. Thus, solubility parameters based on our experimental values are low by about 30 percent. From this and previous work on linear alkanes, it is concluded that in the molecular vaporization process, the large organic molecules studied evaporate approximately as spheres and hence low values for the energy of vaporization are obtained. Consequently, the difference between our experimental energy and that estimated from solubility parameters is the energy for extending the molecule in a vacuum environment.