The preparation of quinolines and related fused-ring heterocycles from the dianions of benzoylacetone,certain cyclic ketone oximes,or certain substituted hydrazones

C(α),O-Dilithiooximes, C(α),N-dilithiobenzoylhydrazones, or C(α),N-dilithiocarboalkoxyhydrazones were prepared in an excess of lithium diisopropylamide (LDA) and condensed with 2-aminobenzophenones, or isatoic anhydrides to give intermediates that were treated with aqueous acid, which caused their hydrolysis, cyclodehydration and/or linear dehydration to give products which were substituted quinolines or related fused-ring heterocycles (e.g., cycloheptaquinolines). Dilithiobenzoylacetone was condensed with 2-aminobenzophenones, which was followed by acid cyclodehydration to substituted 2-phenacylquinolines.     

Synthesis and Properties of Fused‐Ring‐Expanded Porphyrins that were Core‐Modified with Group 16 Heteroatoms

The synthesis of a series of novel core‐modified and fused‐ring‐expanded tetraphenylporphyrins is reported. Theoretical calculations and magnetic circular dichroism (MCD) and fluorescence spectroscopic measurements were used to analyze the effect of core modification with Group 16 oxygen, sulfur, selenium, and tellurium atoms on the optical properties and electronic structures of the porphyrins. Marked redshifts of the Q and B bands and accelerated intersystem‐crossing rates were observed, thus making these compounds potentially suitable for use in a variety of applications. The scope for further fine‐tuning of these optical properties based on additional structural modifications, such as the incorporation of fused benzene rings to form ABAB structures by using a thiophene precursor with a fused bicyclo[2.2.2]octadiene ring and the introduction of various substituents onto the meso‐phenyl rings, is also examined.     

Biohybrid microarrays--impedimetric biosensors with 3D in vitro tissues for toxicological and biomedical screening

To investigate the effectiveness of potential anticancer therapeutics or therapies, efficient screening methods are required. On the one hand, multicellular 3D aggregates (spheroids) are a powerful in vitro model for simulating the in vivo situation and on the other hand, planar electrode structures are generally highly suitable for automation and parallel testing. Here, the detection of the effect of active substances on spheroids positioned on electrodes of substrate integrated electrode arrays is exemplarily investigated. As a 3D tissue model a reaggregation system of T47D clone 11 tumor cells is used. The effect of cytotoxins (DMSO, Triton X-100) on spheroids can be detected by recording the effective impedance of planar electrodes covered by spheroids. The equivalent circuit model parameter of electrodes covered by cytotoxin treated spheroids are determined from recorded impedance spectra and compared to the parameter of electrodes covered by control spheroids as well as not covered electrodes. Spheroids on electrodes mainly influence the electrode impedance in the frequency range of 10 kHz to 1 MHz. The results are discussed in view of an optimal electrode/spheroid-interface for sensing the effects of therapeutics with high sensitivity.     

Integrated mechanism for the morphological structure development in HDPE melt‐blown and machine‐direction‐oriented films

The morphologies of a series of blown films and machine‐direction‐oriented (MDO) films, all produced from high density polyethylene, were characterized. In the blown film process, the crystalline morphology develops while the melt is under extensional stress. In the MDO process, drawing takes place in the solid state and deforms the crystalline morphology of the starting film. The films were characterized by wide‐angle X‐ray scattering (WAXS), small‐angle X‐ray scattering (SAXS) and atomic force microscopy to determine the lamellar morphology. The effect of the type of deformation on the lamellar morphology was studied and relationships were developed between the lamellar and polymer chain morphology using SAXS and WAXS. Blown and MDO films were found to have very different morphologies. However, an integrated mechanism was developed linking the sequential events in the deformation and morphology development in blown and MDO films. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 1834–1844, 2007     

Bacterial interactions with proteins and cells relevant to the development of life-threatening endocarditis studied by use of a quartz-crystal microbalance

Implant-related infections are a major challenge in clinical routine because of severe complications, for example infective endocarditis (IE). The purpose of this study was to investigate the real-time interaction of S. gordonii with proteins and cells important in the development of IE, in a flow system, by use of a quartz-crystal microbalance (QCM). Acoustic sensors were biologically modified by preconditioning with sterile saliva, platelet-poor plasma (PPP), or platelet-rich plasma (PRP), followed then by perfusion of a bacterial suspension. After perfusion, additional fluorescence and scanning electron microscopic (SEM) studies were performed. The surface structure of S. gordonii was analyzed by atomic force microscopy (AFM). Compared with S. gordonii adhesion on the abiotic sensor surface following normal mass loading indicated by a frequency decrease, adhesion on saliva, PPP, or PRP-conditioned sensors resulted in an increase in frequency. Furthermore, adhesion induced slightly increased damping signals for saliva and PPP-coated sensors but a decrease upon bacterial adhesion to PRP, indicating the formation of a more rigid biofilm. Microscopic analysis confirmed the formation of dense and vital bacterial layers and the aggregation of platelets and bacteria. In conclusion, our study shows that the complex patterns of QCM output data observed are strongly dependent on the biological substrate and adhesion mechanisms of S. gordonii. Overall, QCM sheds new light on the pathways of such severe infections as IE.     

The objective assessment of lifetime cumulative ultraviolet exposure for determining melanoma risk

Exposure to ultraviolet radiation has commonly been recognized as the most important environmental risk factor for melanoma. The measurement of UV exposure in humans, however, has proved challenging. Despite the general appreciation that an objective metric for individual UV exposure is needed to properly assess melanoma risk, little attention has been given to the issue of accuracy of UV exposure measurement. The present research utilized a GIS based historical UV exposure model (for which the accuracy of exposure estimates is known) and examined, in the case-control setting, the relative importance of UV exposure compared to self-reported time spent outdoors, in melanoma risk. UV estimates were coupled with residential histories of 820 representative melanoma cases among non-Hispanic white residents under 65 years of age from Los Angeles County and for 877 controls matched to cases by age, sex, race, and neighborhood of residence, to calculate the cumulative lifetime UV exposure and average annual UV exposure. For historical measures, when the participants resided outside the US, we also calculated UV estimates. While there was no increased risk of melanoma associated with self-reported time spent outdoors, the association between annual average UV exposure based on residential history and melanoma risk was substantial, as was the association between cumulative UV exposure based on residential history and melanoma. The time spent in outdoor activities appeared to have no significant effect on melanoma risk in any age strata, however, when adjusted for UV exposure based on residential history, time spent outdoors during young age significantly increased risk for melanoma. While there was some attenuation of risk when we excluded data from people resident overseas (as all other studies we are aware of have done), this did not significantly impact subsequent risk estimates of UV exposure on melanoma.     

Environmental controls of UV-B radiation in forested streams of northern Michigan

We examined UV-B radiation flux and its environmental control within and among streams of northern Michigan. UV-B flux was estimated in streams by plastic dosimetry strips, which allow for the simultaneous and repeated in situ measurement of solar radiation. During the summer of 2004, UV-B flux was measured across depth gradients and along longitudinal transects in seven streams, which were chosen to encompass a range of dissolved organic carbon (DOC) concentrations and canopy cover. Attenuation coefficients of UV-B (K(d) (UV-B)) were estimated using plastic dosimeters placed along a depth gradient. K(d UV-B) were positively correlated with DOC concentration and similar to values obtained with laboratory and in situ spectrometry. Along 100 m longitudinal transects, UV-B flux varied along all streams regardless of their canopy cover and DOC concentration. Within-stream fluxes of UV-B were correlated to canopy cover in the only two streams that both had relatively low DOC concentration and variable canopy cover. Large differences were found among streams in the average UV-B flux (corrected for incident solar flux) reaching the dosimeters at 5 cm depth. These among-stream differences were largely accounted for by the stream width, canopy cover, and DOC concentration. Our results illustrate an inherent variability in UV-B flux within and among streams of northern Michigan that is strongly tied to the interactions of DOC concentration, stream size and riparian vegetation.     

Quantitative imaging of protein adsorption on patterned organic thin-film arrays using secondary electron emission

Secondary electron emission is developed as a means to quantify and image protein binding to Au surfaces modified with patterned organic thin-film arrays. Alkane thiols were patterned via microcontact printing on gold, and their effects on the secondary electron (SE) yield of the surface, systematically quantified. We show that a self-assembled monolayer (SAM) of hexadecane thiol significantly increases the SE yield over the native gold surface, a yield that increases as a function of alkane chain length (C8-C16). This effect is linearly correlated with the surface potentials and wetting properties of these SAMs. Surface layers comprised of poly(ethylene glycol) (PEG) grafted polyacrylamide polymers behave differently, affecting the SE yield by attenuation according to the polymer thickness. These results demonstrate the relative contributions of factors related to the adsorbate molecular structures that serve to strongly mediate the SE yield, providing a foundation for exploiting them as a quantitative electron imaging probe. The latter capability is demonstrated using a model microfluidic assay in which a series of proteins was spatially addressed to a SAM-based pixel array. The gray scale contrasts seen with protein adsorption are directly correlated with both protein molecular weight and mass coverage. These methods are used in two model protein assay experiments: (1) the measurement of the concentration dependent adsorption isotherm for a model protein (fibrinogen); and (2) the selective recognition of a biotinylated protein layer by avidin. These results demonstrate a unique approach to imaging protein binding processes on surfaces with both high analytical and spatial sensitivity.