Subcellular localization of early biochemical transformations in cancer-activated fibroblasts using infrared spectroscopic imaging

The tumor microenvironment, or stroma, is chemically and morphologically modified during carcinoma progression. The predominant cell type in the stroma, the fibroblast, maintains collagen properties in normal tissue and often transformed during tumor progression. Biochemical changes within fibroblasts upon initial cancer activation, however, are relatively poorly defined. Here, we hypothesized that Fourier transform infrared (FT-IR) spectroscopic imaging could potentially be employed to examine these early transformations. Further, we employ attenuated total reflectance (ATR) microscopy to characterize subcellular spectra and their changes upon transformation. We characterized fibroblast transitions upon stimulation with both a molecular agent and a carcinoma-mimicking cellular co-culture system. Changes were predominantly observed in the 1080 cm(-1) and 1224 cm(-1) peak absorbance, commonly associated with nucleic acids, as well as in the band at 2930 cm(-1) associated with the C-H stretching of proteins in the cytoplasmic compartment. In conclusion, biochemical changes in cancer-associated fibroblasts that express α-SMA are dominated by the cytoplasm, rather than the nucleus. This ensures that spectral changes are not associated with proliferation or cell cycle processes of the cells and the cells are undergoing a true phenotypic change denoted by protein modifications in the cell body.     

Characterization of porcine skin as a model for human skin studies using infrared spectroscopic imaging

Porcine skin is often considered a substitute for human skin based on morphological and functional data, for example, for transdermal drug diffusion studies. A chemical, structural and temporal characterization of porcine skin in comparison to human skin is not available but will likely improve our understanding of this porcine skin model. Here, we employ Fourier transform infrared (FT-IR) spectroscopic imaging to holistically measure chemical species as well as spatial structure as a function of time to characterize porcine skin as a model for human skin. Porcine skin was found to resemble human skin spectroscopically and differences are elucidated. Cryo-prepared fresh porcine skin samples for spectroscopic imaging were found to be stable over time and small variations are observed. Hence, we extended characterization to the use of this model for dynamic processes. In particular, the capacity and stability of this model in transdermal diffusion is examined. The results indicate that porcine skin is likely to be an attractive tool for studying diffusion dynamics of materials in human skin.     

Computational studies of room temperature ionic liquid-water mixtures

Room temperature ionic liquids (IL) have been used in numerous applications in chemistry. Addition of water alters many of their properties making it possible to custom design solvents for specific applications. Along with experiments, computational studies using various approaches have provided key insights into the structure and dynamics of IL systems, as well as aggregate formation and phase behavior of the IL/water mixtures. These systems provide computational challenges since ILs and IL/water mixtures are viscous liquids with intrinsically slow processes and structural organization over surprisingly large length scales, which push the limits of applicability of the available techniques. Recent developments in the studies of IL/water mixtures using computational methodologies are reviewed and the future prospects for the field are briefly discussed.     

Dissociative electron attachment to H2S probed by ion momentum imaging

The dissociation dynamics of negative ion resonance states in H(2)S formed upon electron attachment are studied using momentum imaging of the fragment H(-) and S(-) ions and compared with similar resonances in water. The H(-) momentum images show that dissociation dynamics at the 5.2 eV resonance are very similar to those of the 6.5 eV (B(1)) resonance in water. Unlike the 8.5 eV resonance in water, which has A(1) symmetry but is found to display considerable deviation from the axial recoil approximation in the momentum distribution of H(-) ions, the distribution from the corresponding resonance in H(2)S at 7.5 eV is found to follow the axial recoil approximation fairly well. The resonance state with B(2) symmetry at 10 eV is found to decay via four dissociation channels viz.-H(-) + H + S, H(-) + SH(A(2)Σ), H(-) + SH(X(2)Π) and S(-) + H + H channels, similar to those that were seen in the B(2) resonance in water at 12 eV, including sequential fragmentation in the multiple fragmentation channels. However, the angular distributions for the fragment ions from this resonance are found to be distinctly different from those in water, even while displaying considerable deviation from the axial recoil approximation similar to that in water.     

On the integration of data and mathematical modeling languages

This paper examines ways in which the addition of data modeling features can enhance the capabilities of mathematical modeling languages. It demonstrates how such integration is achieved as an application of the embedded languages technique proposed by Bhargava and Kimbrough [4]. Decision-making, and decision support systems, require the representation and manipulation of both data and mathematical models. Several data modeling languages as well as several mathematical modeling languages exist, but they have different sets of these capabilities. We motivate with a detailed example the need for the integration of these capabilities. We describe the benefits that might result, and claim that this could lead to a significant improvement in the functionality of model management systems. Then we present our approach for the integration of these languages, and specify how the claimed benefits can be realized.The author's work on this paper was performed in conjunction with research funded by the Naval Postgraduate School.     

Doped nanocrystalline materials — Physics and applications

The properties and applications of nanocrystals doped with transition and rare-earth impurities are reviewed. The high efficiency and ultrafast recombination times observed in these doped nanocrystals make these materials very attractive for optoelectronic applications.     

Pricing under quality of service uncertainty: Market segmentation via statistical QoS guarantees

This article examines how performance-contingent pricing schemes with long-term statistical performance guarantees can be applied to many IT services. We study two forms of performance-contingent pricing, with rebate proportional to failure rate and fixed rebate for below-threshold performance. We show that threshold-performance contingency pricing can increase both profits and fairness (customers who receive higher benefits pay higher effective price) relative to standard pricing. But an even better solution is to offer a menu of performance guarantees: this can increase the firm’s profit and segment the market. Only service providers whose performance level is sufficiently better than the industry standard can benefit from this pricing mechanism.     

Mixed convective non-steady 3-dimensional micropolar fluid flow at a stagnation point

The problem of mixed convective non-steady three dimensional flow of a micropolar fluid near the stagnation point of a blunt nosed body has been discussed. The governing set of differential equations are solved using the Finite Element Method. The velocity and microrotation distribution are shown graphically to depend upon four parameters namely the micropolar parameter, Grashof number, buoyancy parameter and the degree of acceleration. The conclusions are quite interesting from the application point of view. Received on 4 June 1997