XUV digital in-line holography using high-order harmonics

A step towards a successful implementation of timeresolved digital in-line holography with extreme ultraviolet radiation is presented. Ultrashort XUV pulses are produced as high-order harmonics of a femtosecond laser and a Schwarzschild objective is used to focus harmonic radiation at 38 nm and to produce a strongly divergent reference beam for holographic recording. Experimental holograms of thin wires are recorded and the objects reconstructed. Descriptions of the simulation and reconstruction theory and algorithms are also given. Spatial resolution of few hundreds of nm is potentially achievable, and micrometer resolution range is demonstrated.Comment: 8 pages, 8 figure

Chromatin structural changes precede replication in initiated replicons during inhibition of DNA elongation

Partial inhibition of replicative DNA synthesis by hydroxyurea or other agents produces changes in the composition and structure of bulk chromatin. We have begun to investigate the structural changes in specific regions of the genome using synchronized cells and cloned genomic probes. Current results indicate changes in chromatin structure occur preferentially in initiated replicons and can precede the replication fork during inhibition of DNA elongation. 4 refs., 2 figs

Inducible protective proteins: a potentially novel approach to chemotherapy

A number of toxic chemical and physical agents elicit the induction of a series of protein species, some of which react with the agents and render them non-toxic. A few of the induced species (e.g., metallothionein) are rich in thiol groups which might be expected to react with alkylating agents and render them non-toxic. If a safe means could be found for selectively enhancing the synthesis of alkylating agent-reactive species in normal but not tumor cells, such a procedure would have ramifications in the area of cancer chemotherapy. In this report, we have utilized a variety of trace elements (Zn, Se, Cu, As) as inducers of synthesis of protective species in line CHO Chinese hamster cells and in a number of derived variants to determine whether this type of approach can be utilized to increase resistance to alkylating agent toxicity. Our results indicate that Zn, Se, and Cu elicit a protective response (increased survival) against the toxic effects of iodoacetate or melphalan, and, at least in the case of zinc, at levels which are physiologically reasonable. Arsenite appears to be a marginally effective inducer in the CHO cell. The increased survival is not attributable to metallothionein inducibility, decreased availability of the alkylating agent in the medium or decreased uptake of the drug into the trace element-pretreated cells. The protective responses induced by zinc or selenite alone are additive in cells receiving both trace element prior to exposure to alkylating agent which suggests that different domains of response are elicited by the two metals. Based upon reported differences in inducibility of protective proteins between normal and tumor cells, a possibility is raised for a novel approach to alkylating agent chemotherapy, somewhat analogous to the protocol utilized in high dose methotrexate therapy