X-ray Damage to CF3CO2-Terminated Organic Monolayers on Si/Au: Principal Effect of Electrons.

The relative importance of x-rays alone and of x-ray-generated primary and secondary electrons in damaging organic materials was explored by use of self-assembled monolayers (SAMs) on multilayer thin-film supports. The substrates were prepared by the deposit of thin films of silicon (0, 50, 100, and 200 angstroms) on thick layers of gold (2000 angstroms). These systems were supported on chromium-primed silicon wafers. Trifluoroacetoxy-terminated SAMs were assembled on these substrates, and the samples were irradiated with common fluxes of monochromatic aluminum K(alpha) x-rays. The fluxes and energy distributions of the electrons generated by interactions of the x-rays with the various substrates, however, differed. The substrates that emitted a lower flux of electrons exhibited a slower loss of fluorine from the SAMs. This observation indicated that the electrons-and not the x-rays themselves-were largely responsible for the damage to the organic monolayer.

Imaging of features on surfaces by condensation figures.

Condensation of a vapor to a liquid on a cold surface that is not wet completely by this liquid leads to the formation of an array of droplets. If the surface is heterogeneous in its physical properties (especially its interfacial free energy), the patterns of these arrays reflect this heterogeneity. The distribution of droplets of water (condensation figures or CFs) observed by optical microscopy on a surface can be correlated with the molecular structure of that surface. The substrates used to investigate the formation and morphology of the CFs were patterned, self-assembled monolayers of different alkanethiolates on gold and of alkyl siloxanes on glass. Analysis of CFs is a valuable nondestructive technique for characterizing heterogeneities in surfaces.

Pharmacologic profiling of transcriptional targets deciphers promoter logic.

The blueprint for cellular diversity and response to environmental change is encoded in the cis-acting regulatory sequences of most genes. Deciphering this 'cis-regulatory code' requires multivariate data sets that examine how these regions coordinate transcription in response to diverse environmental stimuli and therapeutic treatments. We describe a transcriptional approach that profiles the activation of multiple transcriptional targets against combinatorial arrays of therapeutic and signal transducing agents. Application of this approach demonstrates how cis-element composition and promoter context combine to influence transcription downstream of mitogen-induced signaling networks. Computational dissection of these transcriptional profiles in activated T cells uncovers a novel regulatory synergy between IGF-1 and CD28 costimulation that modulates NF-kappaB and AP1 pathways through signaling cascades sensitive to cyclosporin A and wortmannin. This approach provides a broader view of the hierarchical signal integration governing gene expression and will facilitate a practical design of combinatorial therapeutic strategies for exploiting critical control points in transcriptional regulation.